Chemie

Ingenieur Review 1665

Technik

Gas Fermentation Expands the Scope of a Process

Network for Material Conversion
Bertram Geinitz{, Aline Hüser{, Marcel Mann{, and Jochen Büchs*
DOI: 10.1002/cite.202000086
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.

Supporting Information
available online

Biotechnological fermentation is a well-established process, however, it is far from being fully understood and exploited. A
new area of fermentation technology that has evolved over the recent decades is gas fermentation. Many microorganisms
have been reported in literature to be capable of utilizing a variety of gases such as CO, CO2, H2, and CH4 under
anaerobic or aerobic conditions as their main carbon and/or energy source. Mostly waste stream gases from industrial
plants or those that can be produced via the gasification of solids are investigated. This review focuses on the currently
available scientific knowledge about gas fermentation processes, particularly anaerobic syngas fermentation and aerobic
methane fermentation. Gas fermentation processes are compared with aerobic and anaerobic fermentation processes based
on dissolved solid substrates. Also, the potential of gas fermentation when integrated into a biotechnological network of
processes is outlined.
Keywords: C1 gas conversion, Fermentation technology, Gas fermentation, Material conversion network,
Renewable resources
Received: April 19, 2020; revised: September 08, 2020; accepted: September 09, 2020

1 Introduction substrates (LDSS fermentation) such as carbohydrates.

Climate goals that aim to reduce greenhouse gas emissions
by 40 % of the greenhouse gas emissions since 1990 by 2030
are a challenge for the European industry and citizens. To
maintain current lifestyles, new technological advances and
strategies in providing alternative resources are needed [1].
To fulfill the goal of a climate neutral industry by 2050 [2],
the reduction of industrial carbon dioxide (CO2) emissions
needs to take place at a rate of 8 % per year. In 2019, 882
European emission-intensive companies responsible for
emitting 3.2 Gt of equivalent carbon dioxide (GtCO2e), have
reported investments worth 124 billion euros in new low-
carbon strategies [3]; 50 % of these investments are from
the transportation sector, 38 % from the energy sector, and
5 % from the materials sector. To reach the climate goals,
there is an urgent need for the implementation of processes
that contribute to emission reduction. Among the numer-
ous approaches for reducing emissions, gaseous substrate
fermentation is a flexible platform that can prevent the
–
emission of fossil carbon and contribute to improved
carbon circularity.
The products produced from current fermentation pro-
cesses range from drugs for medical applications to bulk
chemicals and fuels [4–6]. These fermentation processes are
mostly based on the liquid fermentation of dissolved solid
Some prominent examples of these fermentation processes
are the process wherein first-generation ethanol is produced
from corn, acetone-butanol-ethanol (ABE) fermentation
generating acetone, butanol, and ethanol from glucose as
well as the process producing insulin. The biological routes
of fermentation, in comparison to chemical routes, often
offer advantages in terms of high product specificity, mild
operating conditions, high tolerance to feed stock contami-
nants, and feedstock flexibility. An evolving fermentation
technology, which has engaged the scientific community
and industry, is the liquid fermentation of gaseous sources
(LGS fermentation). LGS fermentation is based on the
microbial utilization and conversion of gaseous substrates
such as carbon monoxide (CO), carbon dioxide (CO2), hy-
drogen (H2), and methane (CH4). LGS fermentation is
highly flexible with respect to feedstock sources. Industrial
waste gases can be used as substrate if sufficient amounts of
1
Bertram Geinitz, Aline Hüser, Marcel Mann,
Prof. Dr.-Ing. Jochen Büchs
jochen.buechs@avt.rwth-aachen.de
RWTH Aachen University, AVT – Biochemical Engineering, For-
ckenbeckstraße 51, 52074 Aachen, Germany.
{
These authors contributed equally

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H2, CO, or CH4 are present. Municipality wastes, other
wastes such as biomass from agriculture and forestry and
energy crops, can be gasified using methods such as gasifi-
cation [7]. Gases can then be converted via LGS fermenta-
tion. Surplus electricity that is generated from renewable re-
sources can be utilized for the production of hydrogen,
which can be added as an energy source for increasing CO2
conversion in LGS fermentation. Hence, LGS fermentation
is a promising technology for a sustainable bioeconomy.
The potential is shown by the operation of pilot and com-
mercial plants as run by LanzaTech Inc., which utilize gas-
eous waste streams from the steel industry [8, 9]. On a non-
commercial level, the use of other gasified waste streams in
LGS fermentation has already been reported, including sew-
age sludge [10], landfills [11], and lignocellulosic biomass
[12, 13]. At present, there are numerous of published stud-
ies describing various details of syngas fermentation and
many biological and technical aspects have been summa-
rized in several reviews [14–22].
This review focuses on the integration of LGS fermenta-
tion into a network of process routes. Material conversion
steps that could benefit from LGS fermentation are em-
phasized. Additionally, currently publicly available scien-
tific knowledge about gas fermentation processes is cate-
gorized and outlined. Furthermore, the basics of LGS
fermentation processes are compared to LDSS fermenta-
tion such that the generally available knowledge about
LDSS fermentation is considered and applied for LGS fer-
mentation whenever applicable. The limited products that
can be produced from LGS fermentation are summarized
in this review and different approaches for tackling this
limitation are outlined.
2 Advantages of an Extended Network of
Process Routes for Gas Fermentation
LGS fermentation as a building block is centered in a net-
work of different conversion processes wherein various sub-
strates, pretreatment, and possible subsequent fermentation
methods are linked (Fig. 1). Potential links might not be
easily identified when investigating LGS fermentation as an

Figure 1. Extended network of thermal, fermentative, and electrochemical material conversions. Potential substrate routes in liquid
fermentation with gaseous substrates (LGS fermentation) (– –), substrate routes in liquid fermentation with dissolved solid sub-
strates (LDSS fermentation) (), possible routes wherein CO2 can be used as an LGS fermentation substrate (—) and product routes
(–  –).

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isolated process. A detailed discussion of the network is
provided after a summary.
As shown in Fig. 1, LGS fermentation processes are
placed at the center of the schematic diagram. LGS fermen-
tation processes are divided into synthesis gas (syngas) fer-
mentation (CO, CO2, H2) (Fig. 1, N [23]) and methanotro-
phic fermentation (CH4 + O2) (Fig. 1, M [24]); they are
capable of using a variety of substrates, including waste
streams, from other processes that would otherwise be
burned or disposed of at cost. Waste streams can either be
gaseous (Fig. 1, C and D [25]) or of solid origin (Fig. 1, A
and B), with the latter requiring pretreatment (Fig. 1, G and
H [12, 26, 27]). Excess electricity (Fig. 1, E) can be used for
the production hydrogen (Fig. 1, J [28]), which is an elec-
tron donor in LGS fermentation. Furthermore, excess elec-
tricity can be used to convert CO2-rich waste gases (Fig. 1,
D) into syngas (Fig. 1, I) [29].
In addition to feedstock flexibility, the feasible strategies
and advantages of extending the product range are depicted
in Fig. 1. The limited product range of LGS fermentation
(Fig. 1, Q) can be circumvented when using LGS products
such as acetate, formate, and methanol as substrates for
LDSS fermentation processes (Fig. 1, L and O). LDSS fer-
mentation offers a wide spectrum of products, ranging from
those that can be used by the medical sector to biofuels
(Fig. 1, P)
In the following chapters, the advantages and disadvan-
tages of various substrate conversion routes are discussed
(Sect. 2.1). Furthermore, syngas fermentation and methano-
trophic fermentation are explained in more detail through
an analysis of publicly available information (Sect. 2.2.1).
Basic technological approaches are described in Sect. 2.2.2
and 2.2.3, and LGS fermentation is compared to LDSS fer-
mentation in Sect. 2.3. The principles that were obtained
during the development of LDSS fermentation can be inte-
grated into LGS fermentation and are described through the
comparison. Finally, the products of LGS fermentation with
emphasis on the advantages of combining different technol-
ogies are discussed in Sect. 2.4 and summarized in Fig. 1.
2.1 Substrate Routes for the Liquid Fermentation
of Gaseous Substrates
2.1.1 Sources of Renewable Gaseous Substrates
Fossil resources such as coal, crude oil, and natural gas have
a well-known and relatively uniform chemical composition,
making them relatively easy to process, (e.g., rectification).
Fossil fuels take thousands of years to develop, whereas
renewable biomass can be derived from any type of plant
and grow back within years or centuries [30]. Compared to
fossil resources, biomass has a chemically diverse structure;
the composition of biomass depends strongly on its origin
and harvest. Currently, most renewable resources that are
processed via fermentation originate from food crops or
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energy plants (Fig. 1, A). After enzymatic hydrolysis, which
may be preceded by thermochemical pretreatment (Fig. 1,
F), the resulting easily accessible carbohydrates are con-
verted by microorganisms via LDSS fermentation (Fig. 1, L)
[31]. However, biomass can originate from many carbon-
containing waste streams originating from the food indus-
try, forestry, agriculture, household, or livestock farming
(Fig. 1, B). Due to its vast diversity, the composition of bio-
mass varies depending on their origin, the climate where
they were produced, and available mixtures [32]. Breaking
down complex mixtures of recalcitrant biomass and utiliz-
ing all its energy and carbon are challenging. Nonetheless,
various alternative routes that are biological, chemical, or
physical have been reported [33, 34]. The downside of
chemical or physical routes is that solvents or acids are
often required for biomass pretreatment, which implies the
inclusion of additional purification steps. Furthermore,
energy-intensive heating, agitation, and recovery are often
required. In a study, Wei et al. calculated the conversion
efficiency of ethanol from hardwood [35]. Gasification with
subsequent microbial conversion has been reported to result
in 40 % higher energy and carbon yield than gasification
techniques that are paired with chemical synthesis.
Prominent routes for syngas (CO, CO2, H2) production
are pyrolysis [26] and gasification [7] (Fig. 1, H). Pyrolysis
is the thermal degradation of an organic substance in the
absence of oxygen at temperatures between 200 and 760 C
[36]. Conventional slow pyrolysis processes produce syn-
thesis gas from volatile compounds, with the non-volatile
compounds remaining as oil and charcoal. Using fast pyrol-
ysis with a high heating rate produces mainly bio oil [37].
The ratio of gas, oil and charcoal depends strongly on the
raw material and the pyrolysis process [27]. In contrast,
gasification occurs at higher temperatures (480–1650 C)
and in the presence of small amounts of oxygen. Aside from
volatile substances, non-volatile substances can also be
completely converted into syngas [36]. Furthermore, bio-
mass can be converted directly into biogas (methanization)
by anaerobic digestion (Fig. 1, G). Microbial communities
enable bioconversion of biomass through a cascade of bio-
chemical steps that achieve final biogas compositions of
approximately 60 % CH4 and 40 % CO2 [38–40]. CH4 gas is
a versatile compound. CH4 originating from natural gas is
currently used as fuel for heat and power generation. After
separating CO2 and impurities such as H2S from biogas, the
remaining biomethane can be easily transported and stored
in the already available natural gas grid. Therefore, it is not
surprising that anaerobic digestion is considered as ‘‘one of
the most attractive renewable energy pathway[s]’’ [40].
2.1.2 Industrial Off-Gas
Different industrial waste gas streams contain valuable sub-
strates such as CO, H2, CH4, and CO2 (Fig. 1, C, D) for LGS
fermentation. Most publications that mention industrial gas
sources for syngas fermentation consider the utilization of
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steel mill exhaust gases suitable [25] (Fig. 1, C). In 2018,
CO2 emissions from the steel industry accounted for 6.7 %
of the global emissions from fossil fuels [41]. Emissions
from the steel industry have different partitions of energy
containing gases, depending on the origin. Coke oven gas
contains 50–70 % H2 and 25–30 % CH4 [42]. Blast furnace
gas contains 5 % H2 and 20 % CO, whereas the gas from the
converter consists of more than 60 % CO [42]. Hence, these
gases are well-suited substrates for syngas fermentation.
Furthermore, coke oven gas can potentially be used as feed-
stock for methanotrophic fermentation. As energy-contain-
ing gases are currently burned to provide electricity for steel
mill operation, the removal of these gaseous resources needs
to be compensated by providing energy from other sources.
In contrast to the steel industry, the cement industry, for
example, emits mainly CO2, containing no energy for bio-
logical conversion. Emissions from the cement industry
account for approximately 8 % of global CO2 emissions
[43]; thus, CO2 from cement factories is a carbon source
that is available in large amounts at local emission sites.
Challenging aspects of the conversion of CO2 as a substrate
are discussed later.
2.1.3 Miscellaneous Residual Carbon Sources
from Other Processes
The utility of lignocellulosic biomass as feedstock (Fig. 1, A)
for industrial LDSS fermentation (Fig. 1, L) is technically
advanced and offers a wide product range (Fig. 1, P). More-
over, the pretreatment processes (Fig. 1, F) that allows the
accessibility of carbohydrates from lignocellulosic biomass
for LDSS fermentation are performed through various
methods [33, 34, 44]. Unfortunately, lignocellulosic biomass
consists of up to 35 % lignin [45], which is a recalcitrant
chemical component that is hardly metabolized by microor-
ganisms [46–48]. Hence, an inherent waste stream contain-
ing valuable carbon is produced from lignocellulosic bio-
mass. This waste stream can be efficiently converted via
pyrolysis (Fig. 1, H) into a valuable gaseous feedstock [49].
2.1.4 Providing Energy Sources for the Utilization
of CO2
The apprehension of climate goals has been reported to be
closely linked to the reduction of greenhouse gas emissions.
LGS fermentation is often considered a technology for
reducing CO2 emissions [6, 50, 51]. However, using CO2 as
the sole feedstock for microbial conversion is not feasible as
CO2 lacks energy content in the form of strong carbon
bonds, electrons, or hydrogen constituent [52]. Further-
more, carbon dioxide, depending on the substrate gas com-
position, may be exhausted as waste gas from LGS fermen-
tation [15].
To provide the energy to reduce CO2 emission, excess
electricity generated from renewable resources is one
option. Here, only processes linked to fermentative conver-
sion routes are mentioned. Excess electricity can be used to
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electrochemically convert CO2 into methanol or formate
[53–55] (Fig. 1, K), which then can be used as a substrate
for fermentation [56] (Fig. 1, O). On the other hand, elec-
tricity can be used to produce hydrogen (Fig. 1, J) or syngas
from CO2 and H2O (Fig. 1, I). Several Power-to-X strategies
aim at the production of H2 or syngas from the excess ener-
gy generated from renewable resources [28, 29]. Hydrogen
can be used to convert carbon dioxide through syngas fer-
mentation [57, 58] (Fig. 1, N). Moreover, hydrogen can be
added to anaerobic digesters for enhanced methane produc-
tion. Through microbial upgrading, CO2 from biogas and
renewable H2 can be converted into CH4 [59, 60] (Fig. 1, G).
In addition to the use of renewable electricity for the pro-
duction of a gaseous substrate, electrofermentation for
increased carbon capture has been reported [61, 62]. Elec-
trofermentation has shown to increase the carbon share
directed towards the target product. Hence, the production
of side products that inherently add to the cost of product
recovery in the downstream process decreases [62, 63]. A
major challenge in electrofermentation is the reactor perfor-
mance. Special reactor designs are required to address
aspects such as surface reaction at the electrodes, liquid-
based bioconversion and electrochemical constraints to
improve the overall performance [64].
2.2 Fundamentals of Liquid Fermentation
of Gaseous Substrates
2.2.1 Status Quo
In 1902, the first microbial conversion of CO was reported
[65]. Since the early 1900s, the microorganisms capable of
utilizing CH4 as the sole carbon source were identified [66].
In 1932, the microbial conversion of H2 and CO2 into acetic
acid was published [67]. After the discovery of gas-ferment-
ing microorganisms, the microbial conversion was not
intensively studied due to the lack of industrial interest.
Until 2010, an annual average of three publications on the
LDS fermentation (see Supporting Information Fig. S1)
have been published. Within the last decade, advanced mi-
crobiological methods, process-engineering strategies, and
the strongly advertised potential of LGS fermentation has
led to an increased industrial and scientific interest. This is
reflected in the increasing number of relevant publications
and reviews (see Supporting Information Fig. S1). Through
a PubMed search, we identified 59 research articles about
LGS fermentation that were published in 2016, which is the
year with the highest annual publication number for the de-
fined criteria. Alongside the vast increase in publications,
the increasing number of reviews has highlighted various
aspects of LGS fermentation. Over the last five years, an
average of eight reviews on LGS fermentation has been pub-
lished per year.
To acknowledge and categorize the available information,
reviews were sorted into different categories (Fig. 2). A
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Figure 2. Categorized published reviews on liquid fermentation with gaseous substrates (LGS): Overview, potential appli-
cation, scale-up, genetic modification, microorganisms, mass transfer, reactor settings, substrates, and products.
variety of fundamental reviews can be found in section
‘‘Overview,’’ which provides easy access to the basics of LGS
fermentation accompanied by a detailed focus on two or
more relevant topics. Under ‘‘Potential applications,’’ review
papers are categorized that investigated the potential of LGS
fermentation for industrial applications. The main applica-
tion is the production of fuels and platform chemicals. In
addition to the examination of the status quo, the exploita-
tion of the potential of various LGS fermentation process
strategies such as multistage process or mixotrophy is
described. The reviews summarized under the section
‘‘Genetic methods’’ examine the genetic engineering poten-
tial of model organisms that are used in LGS fermentation
and provide information on various methods of genetic
modification. Detailed information about the metabolism
and production pathways of common organisms used in
LGS fermentation can be found in the reviews categorized
under the section ‘‘Microorganisms’’. Substrate availability
is a major issue in LGS fermentation and is intensively dis-
cussed in this review. Various reports have mentioned lim-
ited mass transfer of gases as a drawback of LGS fermenta-
tion. This and other issues are addressed and provided
solutions for, such as bubble columns and pressure ferment-
ers, in the reviews listed under ‘‘Mass transfer’’. The section
‘‘Products’’ lists reviews that treat possible products and
their respective stages of development. Moreover, the pro-
duction of C2–C6 alcohols has been reported. The product
spectrum of LGS processes can be widened through optimi-
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zation of different pathways and genetic engineering, or, as
shown in Fig. 1 can be further extended through integration
of LGS-fermentation processes into a network of unit
operations.
2.2.2 Syngas Fermentation
Syngas fermentation is referred to as the microbial conver-
sion of CO-, CO2-, and H2-containing gases. A variety of
potential gas sources are widely available and have been
previously discussed. The microbes with the ability to con-
vert syngas fall primarily into the group of anaerobic
acetogenic bacteria or aerobic carboxydotrophic bacteria
[51, 58, 72, 105].
In this review, syngas fermentation is focused on fermen-
tation using acetogenic bacteria, which employ the Wood-
Ljungdahl pathway. This pathway has been reported to be
one of the oldest CO2 fixation routes and is responsible for
approx. 10 % of the global CO2 fixation [123]. The Wood-
Ljungdahl pathway is well understood and has been
described in detail [124]. A downside of the Wood-Ljung-
dahl pathway is that it results in zero net ATP at substrate-
level phosphorylation. Therefore, ATP generation is solely
based on the transporter systems that are based on proton
gradients [102]. Different proton-translocating systems
have been reported; two prominent systems are the Ferre-
doxin:NAD oxidoreductase (RNF complex) [125] and the
ion-translocating hydrogenase (ECH) mechanism [126].
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The sparsely available energy is a reason for the slow growth
and low metabolic activity of acetogenic microorganisms
[102, 127].
Acetogenic organisms can convert different mixtures of
CO, CO2, and H2 into different products such as alcohols
and acids. The most common products ethanol and acetate
are formed as listed in Tab. 1 (Eqs.(1)–(6)). A comprehen-
sive list of various other products, including some stoichio-
metric reactions, is reported in [51].
Based on the standard Gibbs free energies of the produc-
tion of ethanol and acetate, it is clear that the energy yield
for the organism that produces the said substances is rather
low. In comparison, the combustion of glucose results in a
standard Gibbs free energy of approximately –2800 kJ mol–1
[128]. Additionally, the microorganisms involved in syngas
fermentation show rather slow growth rates and product
formation. For example, in syngas fermentation, the maxi-
mal growth rate of Clostridium ljungdahlii is halved com-
pared to that of the same bacteria on fructose. The ethanol
titer in the LDSS mode is also reduced [129].
Another challenge in syngas fermentation is the produc-
tion of CO2 through a microbial water-gas shift reaction
when organisms are grown on solely CO (Tab. 1, Eq. (7)).
As can be seen from Tab. 1 (Eqs. (1)–(6)) CO conversion is
the most energetically beneficial for microorganisms and
thus, is the preferred metabolic route. Possible solutions for
the utilization of CO2 from syngas with improved efficiency
is by providing additional hydrogen or by using electrofer-
mentation as outlined in Sect. 2.1.4.
Despite the energetic constraints, the first pilot and com-
mercial plants for syngas fermentation are now being uti-
lized. In 2013, three companies (Coskata, INEOS Bio, Lan-
zaTech Inc.) were developing commercial plants for syngas
fermentation [91]. The company Coskata closed in 2015,
Table 1. Most common stoichiometry for ethanol and acetate formation in ace-
togenic microorganisms adapted from Sun et al. [51]. The low changes of the
standard Gibbs free energy underline the low energy yield of the reaction.
Equation Change of standard Gibbs
free energy DG0f [kJ mol–1]
4CO þ 2H2 O fi CH3 COOH þ 2CO2 –154.6
6CO þ 3H2 O fi CH3 CH2 OH þ 4CO2 –217.4
2CO þ 2H2 fi CH3 COOH –114.5
2CO þ 4H2 fi CH3 CH2 OH þ H2 O –137.1
2CO2 þ 4H2 fi CH3 COOH þ 2H2 O –74.3
2CO2 þ 6H2 fi CH3 CH2 OH þ 3H2 O –97.0
CO þ H2 O fi CO2 þ H2 –41.2
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and the knowledge and technology for syngas fermentation
was taken over by Synata Bio. INEOS Bio and LanzaTech
Inc. still exist and run pilot and commercial plants. In addi-
tion to the aforementioned global players, startups such as
Deep Branch Biotechnology from the UK have emerged.
2.2.3 Aerobic Methane Fermentation
Aerobic methanotrophic bacteria can use CH4 as their sole
carbon and energy source [130]. In the detailed review by
Strong and colleagues [24], topics from the natural occur-
rence of methanotrophs to detailed metabolic pathways can
be found. In methanotrophs, methane monooxygenases cat-
alyze the first transformation of CH4 to methanol, thereby
fixing methane in a liquid state; this reaction is oxygen-
dependent [130]. Subsequently, methanol dehydrogenases
convert methanol to formaldehyde. Methanotrophs are sep-
arated into three groups: type I, type II, and type X. In type
I, formaldehyde is subsequently assimilated through the
ribulose monophosphate pathway, whereas in type II meth-
anotrophs, the formaldehyde is subsequently assimilated
through the serine pathway. Type X methanotrophs mainly
utilize the ribulose monophosphate pathway but also pos-
sess enzymes associated with the serine pathway [107].
The potential product spectrum from methanotrophs has
already been extensively reviewed [16, 24, 74–77, 86, 87].
Currently, fundamental research is performed to increase
the titers of intermediates (methanol, formaldehyde, and
organic acids), extracellular polysaccharides, and secondary
metabolites (ectoine, vitamin B12). Furthermore, an in-
creasing number of genetic tools and metabolic network
models for methanotrophs support the current research.
Moreover, polyhydroxybutyrate (PHB) production by
methanotrophs has reached the pilot scale [131]. PHB is the
most studied variant of polyhydroxalkanoates
(PHA). PHB from other sources is already being
used as a recyclable alternative to petrol-based
plastics. The production of methanotrophic
PHA and PHB have been extensively reviewed
[16, 24, 74, 75, 77, 113, 114], though, PHA is not
available on a large scale. In 2013, NewLight
(1)
Technologies announced the successful commis-
sioning of a commercial-scale plant for metha-
(2) notrophic PHA production [132]. Methano-
troph-derived single cell protein as feed for farm
(3) animals marks the product closest to commerci-
alization [84, 116]. According to a press release
(4) in 2019, Unibio announced the commissioning
of a commercial-scale plant in Russia [133]. Fur-
(5) thermore, Calysta has operated a pilot plant to
produce animal feed in England [134]. In 2020,
(6) String Bio announced plans to build a factory
for methane-based protein production in 2020.
(7) Currently, their product is being tested on the
poultry and aquaculture market [135, 136].
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2.3 Liquid Fermentation with Dissolved Solid
Substrates and Gaseous Substrates
Fermentation originates from the Latin word ‘‘fermentum’’
which means the anaerobic conversion of organic matter.
Today, the term fermentation is used generally and
describes any aerobic or anaerobic microbial or enzymatic
conversion of organic matter. Fermentation processes can
be classified either based on their relation to oxygen, i.e.,
aerobic and anaerobic fermentation, or based on its sub-
strate, i.e., LDSS fermentation with a dissolved solid sub-
strate and LGS fermentation with gaseous substrates.
2.3.1 Substrate Availability and Fermentation
Modes
The main difference between LDSS fermentation and LGS
fermentation is the availability and thermodynamic poten-
tial of the substrates that microorganisms can utilize. In
LDSS fermentation, typical substrate concentrations in fer-
mentation media easily reach 200 g L–1. In LGS fermenta-
tion, the maximum substrate availability is limited by the
solubility of the gaseous substrates. Tab. 2 shows the heat of
combustion and maximum solubility of common LGS fer-
mentation substrates with reference to glucose and the
resulting available molar substrate concentration in the
fermentation broth for common substrate supply levels.
According to Tab. 2, the maximum solubility of CH4 in
water at 303.15 K and 1 atm is 1.30 mmol L–1, for CO2
29.99 mmol L–1, for CO 0.92 mmol L–1, and for H2
0.76 mmol L–1. Furthermore, the carbon and energy content
per mole of standard LDSS fermentation substrates are usu-
ally higher than those of LGS fermentation substrates are.
For example, glucose consists of six carbon atoms with a
heat of combustion of approx. 2800 kJ mol–1, which is much
higher than that of carbon monoxide (283 kJ mol–1) with
one carbon atom.
It is evident that LDSS and LGS fermentation have differ-
ent substrate and energy availabilities that lead to different
process requirements. In a study by Wei et al., the conver-
sion efficiencies of ethanol from hardwood by LDSS and
LGS fermentation processes were evaluated [35]. In com-
parison to LDSS, it was found that the 24-hour LGS fer-
Table 2. Relative available molar substrate concentration of dissolved solid and gaseous substrates in the fermentation broth.
Substrate Heat of combustion at 298.15 K Maximum solubility in water at
and 1 atm [kJ mol–1] 303.15 K and 1 atm [mmol L–1]
Glucose 2820 2964
CO 283 0.92
CO2 – 29.99
CH4 889 1.30
H2 286 0.76
O2 – 1.18
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mentation process takes eight times longer than the LDSS
process. This effect is due to the slow microbial growth of
the model organism C. ljungdahlii and limited substrate
availability of gaseous substrates. In contrast, LGS fermen-
tation showed a better product/substrate ratio due to gasifi-
cation efficiency. In this case, it leads to an overall better
energy efficiency than the LDSS fermentation processes,
which are generally carried out in one of the three common
operation modes: batch, fed-batch, or continuous mode.
For anaerobic LDSS fermentation, these terms are used
technically correct. In aerobic LDSS fermentation, these
terms are correctly used only when they refer to the liquid
phase with the dissolved solid carbon source. Oxygen needs
to be continuously supplemented during aerobic LDSS fer-
mentation. Therefore, aerobic LDSS batch or fed-batch fer-
mentation is always continuous when referring to the sup-
plied gas (air). In LGS fermentation, substrates (carbon and
energy source) are soluble only in small quantities (Tab. 2).
Hence, gaseous substrates must be continuously supplied.
The technical term ‘‘batch mode’’ can be used only for
the liquid phase of the fermentation process. Tab. 3
depicts the fermentation modes batch, fed-batch, and con-
tinuous operation mode for anaerobic and aerobic fer-
mentation in relation to the respective state of aggregation
of the substrate.
2.3.2 Respiration and the Challenge in Limited
Gas-Liquid Mass Transfer
In aerobic LDSS fermentation and aerobic and anaerobic
LGS fermentation, the gas-liquid mass transfer of gaseous
substrates is a major challenge. For aerobic LDSS fermenta-
tion, several groups have investigated the influence of oxy-
gen limitation on cultivation [140, 141]. To illustrate the
challenge of providing sufficient oxygen, a simple calcula-
tion can be performed. The complete oxidation of glucose is
given in Eq. (8). A cultivation with an initial glucose con-
centration of 1110 mmol L–1 (200 g L–1) at 30 C and atmo-
spheric pressure, aerated with air containing 21 % oxygen,
was assumed, and the resulting maximum oxygen available
in the liquid phase is approximately 0.25 mmol L–1 [139].
Based on these parameters, the availability of oxygen for the
total conversion of glucose is 26 600 times too low, clearly
Common supply in media Resulting available Ref.
[g L–1] / gas feed [vol %] substrate [mmol L–1]
200 g L–1 1110 [137, 138]
50 % 0.46
50 % 14.99
50 % 0.65 [138, 139]
50 % 0.38
21 % 0.25
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Table 3. Overview of applicable fermentation modes for liquid fermentation with dissolved solid substrate (LDSS fermentation) and liq-
uid fermentation with gaseous substrate (LGS fermentation).
Mode of fermentation Liquid fermentation with dissolved solid substrate
Aerobic
Batch liquid batch
gas continuous
carbon and energy source batch
Fed-Batch liquid fed-batch
gas continuous
carbon and energy source fed-batch
Continuous liquid continuous
gas continuous
carbon and energy source continuous
indicates that a continuous supply of oxygen with a suffi-
cient gas liquid mass transfer is required.
C6 H12 O6 þ 6O2 fi 6CO2 þ 6H2 O
In comparison to O2, the molar solubility of CO and H2
are lower, whereas the solubility of CO2 is approximately 25
times higher (Tab. 2). Nevertheless, the fundamentals and
knowledge of gas-liquid mass transfer in aerobic LDSS can
be integrated into LGS fermentations. For aerobic LDSS fer-
mentation, reactor geometry, headspace-pressure, agitation,
ventilation rate, and several other parameters that can
ensure sufficient oxygen availability have been reported
[142]. Moreover, sufficient ventilation removes evolving
CO2, which could lead to growth inhibitions [141].
Increased agitation, ventilation rate, and fermentation pres-
sure is accompanied by growing costs. Therefore, the
dissolved oxygen concentration needs to be controlled at a
threshold to maintain fermentation conditions suitable for
efficient microbial conversion without unnecessary energy
costs [141, 143].
For LGS fermentation, different research groups have
worked on methods that increase the availability of the gas-
eous substrates for cultivated microorganisms. The effects
of increasing substrate availability have been tested in
serum bottles by either increasing the total headspace pres-
sure or varying the partial pressure of single gas compo-
nents [144–147]. Their results indicated that the gas com-
position in syngas fermentation plays a key role in process
design. At an increased CO partial pressure of 2 atm com-
pared to 0.35 atm, Hurst et al. were able to increase the
maximum bacterial cell concentration of Clostridium car-
boxivorans to approximately 1 g L–1 (440 %). They observed
a shift from non-growth-related ethanol production to
growth-related ethanol production [144]. In a study, a high-
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Liquid fermentation with gaseous substrate
Anaerobic Anaerobic and aerobic
liquid batch liquid batch
gas batch (neglecting exhaust gas) gas continuous
carbon and energy source continuous
liquid fed-batch
not practical
gas batch (neglecting exhaust gas)
liquid continuous liquid continuous (secondary nutrients, co-
feeding)
gas batch (neglecting exhaust gas) gas continuous
carbon and energy source continuous
er CO to H2 ratio has been reported by Jack et al. to result
in a higher overall carbon yield for C. ljungdahlii, while
favoring the production of acetate over ethanol and 2,3-bu-
(8) tanediol [145]. Understanding the effects of different gases
on LGS fermentation processes is crucial in optimizing gas
compositions to achieve a desired product range. In fer-
menter-scale experiments, the influence of an increased
headspace pressure was evaluated [108, 148–150]. Oswald
et al. demonstrated that an increase in pressure of up to
7 bar for LGS fermentations with C. ljungdahlii growing
solely on CO2 and H2 led to a shift in the product spectrum
[149]. At 7 bar, the main product spectrum shifted from
acetate and ethanol to formic acid. When adding CO, an
increased partial pressure of CO in syngas fermentation can
lead to enhanced alcohol production [149]. Pressurized fer-
mentations with CO have been reported to result in unsta-
ble growth performance, product formation, and substrate
consumption [151]. A reason for these findings is the inhib-
ition of hydrogenases in the Wood-Ljungdahl pathway in
cultivations with increased CO partial pressure [23, 151–
154]. Van Hecke et al. listed a number of gas fermentation
processes at elevated pressure, evaluating the overall perfor-
mance of each process [108]. The review summarizes, that
processes benefited from elevated pressures as long as no
inhibiting effects of an increased gas solubility occurred
[108]. Hence, dynamic process control of dissolved gas con-
centrations is demanded to stabilize pressurized LGS fer-
mentations [155]. Van Hecke et al. noted that there remains
a great need for further improvements in product titers and
productivity to enable industrialization [108].
Furthermore, attempts to increase the gas-liquid mass
transfer of CH4, CO2, CO, and O2 via the addition of nano-
particles have also been reported [109, 110]. By supplement-
ing methyl-functionalized silica nanoparticles to syngas
fermentation, the gas transfer of the least soluble H2 was
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increased by 156 % [156]. Nanoparticles can improve
gas-liquid mass transfer for most systems but are also
reported to have a negative effect depending on experimen-
tal conditions [110]. To date, the addition of nanoparticles
is an interesting approach that should be kept in mind.
However, as the corresponding research is still conducted at
the lab scale, the technology is not yet suitable for industrial
process application. Altogether, there is a need for further
research on the stability of nanofluids and the influence of
experimental conditions.
For LDSS fermentations, dynamic process control that
analyzes and adjusts dissolved oxygen concentration is a
well-established standard. Until now, the dissolved gas con-
centrations of CO or H2 cannot be measured by established
online methods. The measurement of the dissolved CO2
concentration is possible with commercial devices but has
not yet been established in syngas fermentation [157]. Due
to the lack of online monitoring, the dissolved gas concen-
tration and substrate availability cannot be dynamically
controlled during LGS fermentation. Currently, reactor
pressures are increased immediately after inoculation
[108, 148, 149]. In aerobic methane fermentations, the influ-
ence of the gas phase composition on the production of
PHB and a lower PHB content resulting from an inhibitory
effect of excess oxygen were reported [147].
It can be concluded that for LGS fermentations, similar
rules that are used for aerobic LDSS fermentations are
applied. Gaseous substrates must be provided in a balanced
manner to supply sufficient substrate at a reasonable cost.
Additionally, in LGS fermentations, there is also the risk of
gaseous substrate inhibition. As demonstrated for aerobic
LDSS fermentation, monitoring and control dissolved gas
concentrations is a powerful tool for successfully running
LDSS fermentation processes. In addition, the monitoring
of dissolved gas concentration in LGS fermentation has
immense potential in increasing further process efficiency
and process understanding.
2.4 Enlarging the Product Spectrum of LGS
Fermentation
The product spectrum of LGS fermentation is currently
limited. In syngas fermentation, simple molecules such as
C2–C8 alcohols and their respective acid products are
formed mainly at product titers far from industrial rele-
vance [35, 68, 72, 158]. Methanotrophic fermentation is still
being developed. A limited product spectrum combined
with low productivity and low titers of valuable products
are the main reasons why many processes of LGS fermenta-
tion are not yet suitable for industrial applications.
Improvements on bacteria at the genetic level and process
optimization are equally important to reach industrializa-
tion but are not highlighted in this review. Genetic engi-
neering approaches have been addressed in several reviews
(Fig. 2). However, this review focuses on the approaches
Chem. Ing. Tech. 2020, 92, No. 11, 1665–1679 ª 2020 The Authors. Published by Wiley-VCH GmbH
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that widen the product spectrum by combining and extend-
ing process techniques. In the following sections, co-cultiva-
tion, mixotrophic approaches, as well as methanol and for-
mate fermentation are discussed in detail.
2.4.1 Simultaneous Co-Cultivation Using Syngas
The co-cultivation of different organisms in a single-stage
process is commonly performed in traditional LDSS fer-
mentation methods. Co-cultivations are applied to widen
product spectrum or utilize different carbon sources [159].
In a study, single-stage co-cultivation of syngas fermenta-
tion that uses the combination of Clostridium autoethanoge-
num with Clostridium kluyveri and C. ljungdahlii with C.
kluyveri has been reported. Both co-cultivations were
reported to result in high-value products (hexanol and octa-
nol) that cannot be produced in a monoculture by the
respective wildtype organisms [17, 160]. The downside of
single-stage co-cultivation is that the same working condi-
tions apply for both microorganisms, which can result in
suboptimal cultivation conditions for each organism. For
example, acetogenic bacteria such as C. autoethanogenum
and C. ljungdahlii are active at pH values of 6 and below,
and C. kluyveri is particularly active at approximately pH 7
[17]. Nevertheless, C. autoethanogenum and C. ljungdahlii
in monocultures cannot produce molecules exceeding C2
bodies. Therefore, in some cases, deviations from optimal
process conditions can be useful. Furthermore, it has been
reported that in co-cultivation, a CO non-tolerant organism
is able to grow in an environment containing CO. The ace-
togenic organism removes CO from the media, providing
niches for C. kluyveri to grow without experiencing signifi-
cant CO exposure [17]. Until now, the production of high-
quality products by co-cultivation in LGS fermentation has
led to product titers far from the level of industrialization.
With the increasing number of genetic tools, the testing of
further biological combinations and ongoing research about
process optimization and co-cultivation may develop into a
promising process route for LGS fermentation in the future.
2.4.2 Cascaded Co-Cultivation Using Syngas
In addition to the single-stage cultivation, a two-stage pro-
cess was designed by Richter et al. to improve ethanol pro-
duction on syngas [161]. In a first reactor (growth stage),
acetogenic conditions are maintained for optimal growth
conditions. At this stage, acetate is mainly produced from
syngas. In a second reactor (production stage), solventogen-
ic conditions are maintained at a lower pH to initiate etha-
nol production. For increased productivity, cell recycling is
performed at the second stage wherein high cell densities
of up to 10 g L–1 cell dry weight are maintained. With this
setup, ethanol concentrations can reach approximately
20 g L–1, resulting in production rates of up to 0.37 g L–1h–1.
Additionally, the acetate formed in the first stage is nearly
completely converted to ethanol in the second stage. The
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high production rates of ethanol combined with the
minimization of unwanted by-products make the two-stage
process promising for the implementation of LGS fermenta-
tions in the industry.
2.4.3 Combination of LGS and LDSS Fermentation
While the product spectrum of LGS fermentation is cur-
rently limited, a broad variety of molecules such as fuels,
platform chemicals, pharmaceuticals, antibiotics, food, and
feed additives can be produced via LDSS fermentation. Dif-
ferent approaches that combine the advantages of cheap
and widely available substrates of LGS fermentation but
with the product spectrum of LDSS fermentation have been
published. In a two-stage process, C. ljungdahlii has been
used to produce acetate from CO2 and H2 in the first stage
(Fig. 1, N), and acetate was subsequently converted into sin-
gle-cell protein through the aerobic fermentation of Saccha-
romyces cerevisiae [162] (Fig. 1, L and P). The resulting ace-
tate production in the first stage reached industrially
relevant rates of 1 g L–1h–1, whereas the ethanol production
rates remained low. In the second stage, promising carbon
yields of 25 % per consumed CO2 were achieved. Another
study also reported the production of malic acid from syn-
gas in a two-stage reaction system. As described earlier, ace-
tate is the intermediate product that is produced from syn-
gas and is further converted into malic acid by Aspergillus
oryzae [163]. The results of this study serve as a proof of
concept that highly valuable products such as L-malate can
be produced from syngas. As acetate is a substrate that is
widely used by many microorganisms, the product spec-
trum can easily be extended by using sequential mixed cul-
tures [17, 160, 164].
2.4.4 Synergistic Co-Feeding of Dissolved Solid
and Gaseous Substrates
Acetogenic organisms have long generation times and low
biomass yields compared to other microorganisms used for
industrial applications; consequently, the conversion rate of
CO and the formation rate of the products are low. This
characteristic has been reported to result from the low ener-
gy yield of the Wood-Ljunhdahl pathway when cultivated
on gaseous carbon and energy sources. To overcome the
energy deficiency and provide additional ATP to acetogenic
organisms, the co-feeding of solid and gaseous carbon sour-
ces was suggested [165]. The substrates for co-feeding
would act as a superior source of ATP and NADPH to sub-
strates such that catabolic repression is avoided and carbon
reduction is synergistically triggered.
In a study, Moorella thermoacetica was fed with CO2 and
glucose as the substrates for co-feeding; this resulted in a
CO2 conversion of 2.3 g (g cell dry weight)–1h–1; to increase
the product value, the produced acetate was further con-
verted to lipids. Lipid production from acetate by Yarrowia
lipolytica has also been enhanced by co-feeding with gluco-
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nate [165]. Furthermore, two more co-feeding approaches
have been reported, thereby indicating the potential oppor-
tunities that co-feeding strategies offer. Xylose, as a sub-
strate for co-feeding, enhanced CO utilization in systems
with C. autoethanogenum [164]. In another study, H2 and
syngas as substrates increased carbon fixation in LDSS fer-
mentation in combination with the use of various Clostridia
strains [166]. The future application of co-feeding may help
overcome energy constraints in LGS fermentation. More-
over, by providing additional energy for the microbial
strains and using acetogenic organisms that employ the
Wood-Ljungdahl pathway, the carbon yield from solid sub-
strates can be increased. The Wood-Ljungdahl pathway is
capable of converting CO2 with additional redox equiva-
lents into acetyl-CoA, which can then be further converted
into various products [167]. CO2 can originate from glucose
consumption. In summary, co-feeding of solid and gaseous
substrates can increase the available energy of microorga-
nisms and thereby result in a reduction of carbon loss in
the form of CO2. Consequently, mixotrophic approaches
may further expand product spectrum and lead to further
efficient carbon utilization. However, a socioeconomic study
is necessary to clarify whether the improvement of the
reduction potential of CO2 justifies higher substrate costs.
2.4.5 Methanol and Formate as Universal Building
Blocks
The liquid C1-compounds, methanol and formate, can be
produced from CO2 by using excess electricity (Fig. 1, K)
[53–55]. Furthermore, as liquids, both C1-compounds are
storable and can decouple the availability of excess energy
from subsequent processes such as fermentation [56]. Addi-
tionally, methanol and formate can be produced in LGS fer-
mentation (Fig. 1, M and N) [95, 149]. Methanol is consid-
ered a key molecule in methane-based biorefinery [95].
Naturally, methanol does not accumulate during methano-
trophic fermentation (Fig. 1, M). Therefore, two challenges
must be overcome. First, the conversion of methanol to
formaldehyde by methanol dehydrogenase must be inhib-
ited [95]; cyclopropanol, NaCl, and NH4Cl were used to in-
hibit MDH activity [168, 169]. Second, the conversion of
CH4 to methanol is dependent upon reduction equivalents.
Without the manipulation of the conversion, the reduction
equivalents are produced through the further oxidation of
methanol. To achieve methanol accumulation, the reduction
equivalents must be provided from alternative sources. To
our knowledge, the highest titer of 1.34 g L–1 methanol was
achieved by using EDTA as a methanol dehydrogenase
inhibitor while simultaneously adding formate such that the
reduction equivalents are regenerated [112]. So far, relative-
ly low productivities and the required regeneration of
reducing agents impede the commercialization of biological
methane-to-methanol conversion [24, 77, 95]. To date,
enzymatic conversion ex vivo is not economical as the
required reduction equivalents are expensive. This obstacle
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 Chemie
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may be overcome by using electrochemical techniques or egorizes current information on gas fermentation such that
enzyme cascades that regenerate the reduction equivalents. existing knowledge on gas fermentation are made easily
To achieve higher methanol titers, a genetic optimization of accessible to researchers and interested readers. LGS fer-
the metabolic pathway may be proposed. Genetic engineer- mentation has been demonstrated as a flexible platform that
ing of methanotrophs is still in its infancy, but the number can utilize waste gas streams from various established pro-
of genetic tools that can be employed is currently increasing cesses that are otherwise difficult to valorize.
[75, 86, 87]. By using metabolic network analysis, critical
bottlenecks can be identified and optimized. Alternatively,
the pathways can be expressed in industrial workhorses Supporting Information
such as E. coli. Unfortunately, this approach is limited by
the expression of fully active methane monooxygenases in Supporting Information for this article can be found under
non-native hosts [86]. Additionally, methanol can be used DOI: https://doi.org/10.1002/cite.202000086.
as a substrate for methylotrophic bacteria, which are a sub-
group of methanotrophs (Fig. 1, O). Consequently, this
leads to a product range that is similar to that produced in We thank the German Federal Ministry of Education
aerobic methane fermentations [170]. and Research (BMBF) for their financial support [grant
According to Cotton and colleagues [56] converting for- numbers 01DQ17012 and 03INT513BE]. Open access
mate instead of gaseous substrates could broaden the product funding enabled and organized by Projekt DEAL.
spectrum of acetogens. Furthermore, the energetic efficiency
of formate conversion is 80–90 %, compared to 60–80 %
H2/CO2 or CO conversion in anaerobic acetogens. Acetogens
Bertram Geinitz studied
are promising candidates for formate conversion as the toxic
Life Science Engineering at
intermediate formaldehyde is not produced [56].
the Friedrich-Alexander
Universität Erlangen-Nürn-
berg (FAU) and received
3 Conclusion
his Master of Science in
2015. Since 2016, he is
Over the last decade, LGS fermentation has attracted the in-
working as a research assis-
terest of science and industry alike. Several research groups
tant at the Chair of Bio-
around the world have started to investigate LGS fermenta-
chemcial Engineering
tion from a scientific standpoint. According to the news
headed by Prof. Jochen
that were released from the world’s leading companies, LGS
Büchs (RWTH Aachen
fermentation pilot plants as well as commercial plants are
University). Bertram Gei-
now being operated successfully and that methane fermen-
nitz focuses on online mon-
tation has already reached commercial scale. LGS fermenta-
itoring tools for cocultures as well as microbial meth-
tion is placed into a network of conversion processes. In
ane utilization.
this review, highlights and future prospects of innovative
approaches that increase the product spectrum of LGS fer-
mentation were discussed. Upgrading acetate from syngas
to more valuable products was outlined as a very promising Aline Hüser studied
route for future application in LGS fermentation. Moreover, Biochemical Engineering at
we highlighted the potential of LGS fermentation of being TU Dortmund. She com-
integrated into networks of conversion processes as it can pleted her studies in 2018
be flexibly used in various conversion routes. Despite the with her master’s thesis at
currently low product titers, the potential of single-stage co- the chair for Thermody-
cultivation processes and the combination of LGS and LDSS namic of Prof. Gabriele
fermentation in producing high-quality products have been Sadowski. After her gradua-
demonstrated. The use of synergistic co-feeding strategies tion, Aline Hüser joined the
to improve CO2 reduction is a novel approach that has been chair for Biochemical Engi-
shown to lead to very promising results. The production of neering as a research assis-
the C1-components of methanol and formate is an intrigu- tant under the supervision
ing approach for reducing greenhouse gases. However, for of Prof. Jochen Büchs at
all process routes discussed, detailed socioeconomic studies RWTH Aachen University.
are necessary to clarify whether the improvements justify Her research focuses on process development for
higher costs and whether the processes are ready for imple- microbial synthesis gas conversion and microbial CO2
mentation in the industry. This review summarizes and cat- utilization.

Chem. Ing. Tech. 2020, 92, No. 11, 1665–1679 ª 2020 The Authors. Published by Wiley-VCH GmbH www.cit-journal.com

1676
Marcel Mann received his
Bachelor degree at the FH
Aachen University of
applied science in 2015. In
2017, he finished his Master
at the RWTH Aachen Uni-
versity by handing in his
research thesis conducted
at the Western University
of Ontario. Since 2018 he is
working as a research assis-
tant at the Chair of Bio-
chemical engineering lead
by Prof. Jochen Büchs
(RWTH Aachen University). Marcel Mann’s research
focuses on process development and online monitoring
devices for syngas fermentation.
Jochen Büchs is head of the
Chair of Biochemical Engi-
neering at the RWTH
Aachen University. His
research is focused on char-
acterization of shaken bio-
reactors, development of
online monitoring devices,
feeding strategies in small
scale and pressure fermen-
tation. Prior to his academ-
ic career, he was head of the
biotechnological pilot plant
of BASF group in Ludwigs-
hafen. Until now, he has published 270 original papers
and filed numerous patents. Several of the chair’s devel-
opments have been successfully commercialized world-
wide.
Abbreviations
ABE fermentation acetone-butanol-ethanol fermentation
acetyl-CoA acetyl coenzym A
ATP adenosin triphosphate
ECH ion translocating hydrogenase
mechanism
GtCO2e giga tons of carbon dioxide equivalents
LDSS liquid dissolved solid substrates
LGS liquid gaseous substrates
MDH methanol dehydrogenase
PHA polyhydroxyalkanoate
PHB polyhydroxybutyrate
RNF complex ferredoxin:NAD oxidoreductase
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Chemie
Review Ingenieur
Technik
syngas gas mixture made of CO, CO2 and H2
as synthetic composition or waste
stream
References
[1] https://ec.europa.eu/clima/policies/strategies/2030_en (accessed
on March 05, 2020)
[2] https://ec.europa.eu/clima/policies/strategies/2050_en (accessed
on March 05, 2020)
[3] www.cdp.net/en/research/global-reports/doubling-down
(accessed on September 07, 2020)
[4] R. A. Weusthuis, I. Lamot, J. van der Oost, J. P. M. Sanders,
Trends Biotechnol. 2011, 29 (4), 153–158. DOI: https://doi.org/
10.1016/j.tibtech.2010.12.007
[5] N. Ferrer-Miralles, J. Domingo-Espı́n, J. Corchero, E. Vázquez,
A. Villaverde, Microb. Cell Fact. 2009, 8, 1–8. DOI: https://
doi.org/10.1186/1475-2859-8-17
[6] A. Fivga, L. G. Speranza, C. M. Branco, M. Ouadi, A. Hornung,
AIMS Energy 2019, 7 (1), 46–76. DOI: https://doi.org/10.3934/
ENERGY.2019.1.46
[7] K. Göransson, U. Söderlind, J. He, W. Zhang, Renewable Sustain-
able Energy Rev. 2011, 15 (1), 482–492. DOI: https://doi.org/
10.1016/j.rser.2010.09.032
[8] www.lanzatech.com/2018/06/08/worlds-first-commercial-waste-
gas-ethanol-plant-starts/ (accessed on March 30, 2020)
[9] https://corporate.arcelormittal.com/media/news-articles/2018-
jun-11-arcelormittal-and-lanzatech-break-ground-on-
150million-project (accessed on March 30, 2020)
[10] Y. Sun, J. Nakano, L. Liu, X. Wang, Z. Zhang, Sci. Rep. 2015, 5,
1–12. DOI: https://doi.org/10.1038/srep11436
[11] www.lanzatech.com/2017/12/07/trash-tank-upcycling-landfill-
fuel-demonstrated-japan/ (accessed on August 18, 2020)
[12] S. Wainaina, I. S. Horváth, M. J. Taherzadeh, Bioresour. Technol.
2018, 248, 113–121. DOI: https://doi.org/10.1016/
j.biortech.2017.06.075
[13] P. C. Munasinghe, S. K. Khanal, Bioresour. Technol. 2010, 101
(13), 5013–5022. DOI: https://doi.org/10.1016/j.bio-
rtech.2009.12.098
[14] S. Redl, M. Diender, T. Ø. Jensen, D. Z. Sousa, A. T. Nielsen, Ind.
Crops Prod. 2017, 106, 21–30. DOI: https://doi.org/10.1016/
j.indcrop.2016.11.015
[15] J. R. Phillips, R. L. Huhnke, H. K. Atiyeh, Fermentation 2017,
3 (2), 28. DOI: https://doi.org/10.3390/fermentation3020028
[16] L. V. Teixeira, L. F. Moutinho, A. S. Romão-Dumaresq, Biofuels,
Bioprod. Biorefin. 2018, 12 (6), 1103–1117. DOI: https://doi.org/
10.1002/bbb.1912
[17] M. Diender, A. J. M. Stams, D. Z. Sousa, Biotechnol. Biofuels
2016, 9 (1), 1–11. DOI: https://doi.org/10.1186/s13068-016-
0495-0
[18] M. Mohammadi, A. R. Mohamed, G. Najafpour, H. Younesi,
M. H. Uzir, Energy Sources, Part A 2016, 38 (3), 427–434.
DOI: https://doi.org/10.1080/15567036.2012.729254
[19] B. Molitor, H. Richter, M. E. Martin, R. O. Jensen, A. Juminaga,
C. Mihalcea, L. T. Angenent, Bioresour. Technol. 2016, 215
(March), 386–396. DOI: https://doi.org/10.1016/
j.biortech.2016.03.094
[20] K. Valgepea et al., Biotechnol. Biofuels 2018, 11 (1), 1–15.
DOI: https://doi.org/10.1186/s13068-018-1052-9
[21] M. Mohammadi, H. Younesi, G. Najafpour, A. R. Mohamed,
J. Chem. Technol. Biotechnol. 2012, 87 (6), 837–843. DOI: https://
doi.org/10.1002/jctb.3712
Chem. Ing. Tech. 2020, 92, No. 11, 1665–1679
 Chemie
Ingenieur Review
Technik
[22] S. Y. Lee, K. S. Mo, J. H. Choi, N. H. Hur, Y. K. Kim, B. K. Oh,
J. Lee, Korean J. Chem. Eng. 2015, 32 (9), 1744–1748.
DOI: https://doi.org/10.1007/s11814-014-0383-x
[23] S. K. Barik, S. Prieto, S. B. Harrison, E. C. Clausen, J. L. Gaddy,
Bioprocess. Biotreat. Coal 2017, 39 (1), 131–154. DOI: https://
doi.org/10.1201/9781315138367
[24] P. J. Strong, S. Xie, W. P. Clarke, Environ. Sci. Technol. 2015,
49 (7), 4001–4018. DOI: https://doi.org/10.1021/es504242n
[25] F. M. Liew, M. Kopke, S. Dennis, in Liquid, Gaseous and Solid
Biofuels – Conversion Techniques (Ed: Z. Fang), InTechOpen,
London 2013. DOI: https://doi.org/10.5772/52164
[26] M. Jahirul, M. Rasul, A. Chowdhury, N. Ashwath, Energies 2012,
5 (12), 4952–5001. DOI: https://doi.org/10.3390/en5124952
[27] D. Mohan, C. U. Pittman, P. H. Steele, Energy Fuels 2006, 20 (3),
848–889. DOI: https://doi.org/10.1021/ef0502397
[28] B. Rego de Vasconcelos, J.-M. Lavoie, Front. Chem. 2019, 7.
DOI: https://doi.org/10.3389/fchem.2019.00392
[29] S. Hernández, A. M. Farkhondehfal, F. Sastre, M. Makkee,
G. Saracco, N. Russo, Green Chem. 2017, 19 (10), 2326–2346.
DOI: https://doi.org/10.1039/C7GC00398F
[30] Biorefineries Targeting Energy, High Value Products and Waste
Valorisation (Eds: M. Rabaçal, A. F. Ferreira, C. A. M. da Silva,
M. Costa), 1st ed., Springer International Publishing, Cham,
Switzerland 2017.
[31] L. Regestein et al., Biotechnol. Biofuels 2018, 11 (1), 1–11.
DOI: https://doi.org/10.1186/s13068-018-1273-y
[32] S. V. Vassilev, D. Baxter, L. K. Andersen, C. G. Vassileva, Fuel
2010, 89 (5), 913–933. DOI: https://doi.org/10.1016/
j.fuel.2009.10.022
[33] P. Vyas, A. Kumar, S. Singh, Front. Biosci., Elite Ed. 2018, 10 (1),
155–174. DOI: https://doi.org/10.2741/e815
[34] D. P. Maurya, A. Singla, S. Negi, 3 Biotech 2015, 5 (5), 597–609.
DOI: https://doi.org/10.1007/s13205-015-0279-4
[35] L. Wei, L. O. Pordesimo, C. Igathinathane, W. D. Batchelor,
Biomass Bioenergy 2009, 33 (2), 255–266. DOI: https://doi.org/
10.1016/j.biombioe.2008.05.017
[36] www.globalsyngas.org/syngas-applications/gasification-vs.-
pyrolysis (accessed on August 23, 2020)
[37] C. Pfitzer, N. Dahmen, N. Tröger, F. Weirich, J. Sauer, A.
Günther, M. Müller-Hagedorn, Energy Fuels 2016, 30 (10),
8047–8054. DOI: https://doi.org/10.1021/acs.energy-
fuels.6b01412
[38] Y. Q. Tang, T. Shigematsu, S. Morimura, K. Kida, J. Biosci.
Bioeng. 2015, 119 (4), 375–383. DOI: https://doi.org/10.1016/
j.jbiosc.2014.09.014
[39] F. Kemausuor, M. Adaramola, J. Morken, Energies 2018, 11 (11),
2984. DOI: https://doi.org/10.3390/en11112984
[40] N. Scarlat, J. F. Dallemand, F. Fahl, Renewable Energy 2018, 129,
457–472. DOI: https://doi.org/10.1016/j.renene.2018.03.006
[41] Steel’s Contribution to a Low Carbon Future and Climate Resilient
Societies, Worldsteel Position Paper, World Steel Assosioation,
Brussels 2017.
[42] www.clarke-energy.com/wp-content/uploads/Steel-Production-
Gases1.pdf (accessed on August 18, 2020)
[43] www.bbc.com/news/science-environment-46455844 (accessed
on March 31, 2020)
[44] J. Baruah, B. K. Nath, R. Sharma, S. Kumar, R. C. Deka, D. C.
Baruah, E. Kalita, Front. Energy Res. 2018, 6. DOI: https://
doi.org/10.3389/fenrg.2018.00141
[45] L. Lin, F. Xu, X. Ge, Y. Li, in Adv. Bioenergy, 5th ed., Elsevier,
Edmonton 2019.
[46] J. B. Kristensen, C. Felby, H. Jørgensen, Biotechnol. Biofuels
2009, 2, 1–10. DOI: https://doi.org/10.1186/1754-6834-2-11
Chem. Ing. Tech. 2020, 92, No. 11, 1665–1679 ª 2020 The Authors. Published by Wiley-VCH GmbH
1677
[47] O. Sanchez, R. Sierra, C. J. Almeciga-Diaz, in Alternative Fuel
(Ed: M. Manzanera), InTechOpen, London 2011. DOI: https://
doi.org/10.5772/22381
[48] R. Shavi, J. Ko, A. Cho, J. W. Han, J. G. Seo, Appl. Catal., B 2018,
229 (January), 237–248. DOI: https://doi.org/10.1016/
j.apcatb.2018.01.058
[49] K. Koido, T. Iwasaki, in Lignin – Trends and Applications (Ed:
M. Poletto), InTechOpen, London 2018.
[50] Q. Zhu, Clean Energy 2019, 3 (2), 85–100. DOI: https://doi.org/
10.1093/ce/zkz008
[51] X. Sun, H. K. Atiyeh, R. L. Huhnke, R. S. Tanner, Bioresour.
Technol. Rep. 2019, 7, 100279. DOI: https://doi.org/10.1016/
j.biteb.2019.100279
[52] E. Alper, O. Yuksel Orhan, Petroleum 2017, 3 (1), 109–126.
DOI: https://doi.org/10.1016/j.petlm.2016.11.003
[53] S. A. Al-Saydeh, S. J. Zaidi, Carbon Dioxide Conversion to Meth-
anol: Opportunities and Fundamental Challenges, 1st ed., InTech,
London 2018.
[54] S. Kar, A. Goeppert, G. K. S. Prakash, Acc. Chem. Res. 2019,
52 (10), 2892–2903. DOI: https://doi.org/10.1021/
acs.accounts.9b00324
[55] S. N. B. Villadsen, P. L. Fosbøl, I. Angelidaki, J. M. Woodley,
L. P. Nielsen, P. Møller, ChemSusChem 2019, 12 (10), 2147–2153.
DOI: https://doi.org/10.1002/cssc.201900100
[56] C. A. R. Cotton, N. J. Claassens, S. Benito-Vaquerizo, A. Bar-
Even, Curr. Opin. Biotechnol. 2020, 62, 168–180. DOI: https://
doi.org/10.1016/j.copbio.2019.10.002
[57] J. Yu, World J. Microbiol. Biotechnol. 2018, 34 (7), 89.
DOI: https://doi.org/10.1007/s11274-018-2473-0
[58] R. Takors, M. Kopf, J. Mampel, W. Bluemke, B. Blombach, B. Eik-
manns, F. R. Bengelsdorf, D. Weuster-Botz, P. Dürre, Microb.
Biotechnol. 2018, 11 (4), 606–625. DOI: https://doi.org/10.1111/
1751-7915.13270
[59] N. Aryal, T. Kvist, F. Ammam, D. Pant, L. D. M. Ottosen, Biore-
sour. Technol. 2018, 264, 359–369. DOI: https://doi.org/10.1016/
j.biortech.2018.06.013
[60] J. De Vrieze, K. Verbeeck, I. Pikaar, J. Boere, A. Van Wijk,
K. Rabaey, W. Verstraete, New Biotechnol. 2020, 55, 12–18.
DOI: https://doi.org/10.1016/j.nbt.2019.09.004
[61] A. Schievano, D. Pant, S. Puig, Front. Energy Res. 2019, 7 (Oct),
1–4. DOI: https://doi.org/10.3389/fenrg.2019.00110
[62] A. Schievano, T. Pepé Sciarria, K. Vanbroekhoven, H. De Wever,
S. Puig, S. J. Andersen, K. Rabaey, D. Pant, Trends Biotechnol.
2016, 34 (11), 866–878. DOI: https://doi.org/10.1016/
j.tibtech.2016.04.007
[63] F. Kracke, J. O. Krömer, BMC Bioinformatics 2014, 15 (1), 1–14.
DOI: https://doi.org/10.1186/s12859-014-0410-2
[64] T. Krieg, J. Madjarov, L. F. M. Rosa, F. Enzmann, F. Harnisch,
D. Holtmann, K. Rabaey, Adv. Biochem. Eng. Biotechnol. 2019,
167, 231–271. DOI: https://doi.org/10.1007/10_2017_40
[65] M. W. Beijerinck, A. van Delden, Zentralbl. Bakteriol. 1903, 10,
33.
[66] E. R. Leadbetter, J. W. Foster, Arch. Mikrobiol. 1958, 30 (1),
91–118. DOI: https://doi.org/10.1007/BF00509229
[67] F. Fischer, R. Lieske, K. Winzer, Biochem. Z. 1932, 245, 2–12.
[68] F. Liew, M. E. Martin, R. C. Tappel, B. D. Heijstra, C. Mihalcea,
M. Kopke, Front. Microbiol. 2016, 7, 694. DOI: https://doi.org/
10.3389/fmicb.2016.00694
[69] O. Tirado-Acevedo, M. S. Chinn, A. M. Grunden, Adv. Appl.
Microbiol. 2010, 70, 57–92. DOI: https://doi.org/10.1016/
S0065-2164(10)70002-2
[70] H. N. Abubackar, M. C. Veiga, C. Kennes, Biofuels, Bioprod. Bio-
refin. 2011, 5 (1), 93–114. DOI: https://doi.org/10.1002/bbb.256
www.cit-journal.com

1678
[71] M. Yasin, Y. Jeong, S. Park, J. Jeong, E. Y. Lee, R. W. Lovitt, B. H.
Kim, J. Lee, I. S. Chang, Bioresour. Technol. 2015, 177, 361–374.
DOI: https://doi.org/10.1016/j.biortech.2014.11.022
[72] J. Daniell, M. Köpke, S. Simpson, Energies 2012, 5 (12), 5372–
5417. DOI: https://doi.org/10.3390/en5125372
[73] S. De Tissera, M. Köpke, S. D. Simpson, C. Humphreys, N. P.
Minton, P. Dürre, in Biorefineries (Eds: K. Wagemann, N. Tipp-
kötter), Springer International Publishing, Cham 2019.
[74] S. Cantera, S. Bordel, R. Lebrero, J. Gancedo, P. A. Garcı́a-Enci-
na, R. Muñoz, World J. Microbiol. Biotechnol. 2019, 35 (1), 1–10.
DOI: https://doi.org/10.1007/s11274-018-2587-4
[75] Q. Fei, M. T. Guarnieri, L. Tao, L. M. L. Laurens, N. Dowe, P. T.
Pienkos, Biotechnol. Adv. 2014, 32 (3), 596–614. DOI: https://
doi.org/10.1016/j.biotechadv.2014.03.011
[76] A. J. Pieja, M. C. Morse, A. J. Cal, Curr. Opin. Chem. Biol. 2017,
41, 123–131. DOI: https://doi.org/10.1016/j.cbpa.2017.10.024
[77] P. Dürre, B. J. Eikmanns, Curr. Opin. Biotechnol. 2015, 35, 63–72.
DOI: https://doi.org/10.1016/j.copbio.2015.03.008
[78] F. R. Bengelsdorf, P. Dürre, Microb. Biotechnol. 2017, 10 (5),
1167–1170. DOI: https://doi.org/10.1111/1751-7915.12763
[79] J. Daniell, S. Nagaraju, F. Burton, M. Kopke, S. D. Simpson, Adv.
Biochem. Eng. Biotechnol. 2016, 156, 293–321. DOI: https://
doi.org/10.1007/10_2015_5005
[80] F. C. F. Baleeiro, S. Kleinsteuber, A. Neumann, H. Strauber, Appl.
Microbiol. Biotechnol. 2019, 103 (21–22), 8689–8709. DOI:
https://doi.org/10.1007/s00253-019-10086-9
[81] B. Acharya, P. Roy, A. Dutta, Biofuels 2014, 5 (5), 551–564.
DOI: https://doi.org/10.1080/17597269.2014.1002996
[82] M. Devarapalli, H. K. Atiyeh, Biofuel Res. J. 2015, 2 (3), 268–280.
DOI: https://doi.org/10.18331/BRJ2015.2.3.5
[83] Y. Jiang, J. Liu, W. Jiang, Y. Yang, S. Yang, Biotechnol. Adv. 2015,
33 (7), 1493–1501. DOI: https://doi.org/10.1016/
j.biotechadv.2014.10.007
[84] A. Ritala, S. T. Häkkinen, M. Toivari, M. G. Wiebe, Front. Micro-
biol. 2017, 8. DOI: https://doi.org/10.3389/fmicb.2017.02009
[85] P. Dürre, FEMS Microbiol. Lett. 2016, 363 (6), fnw040.
DOI: https://doi.org/10.1093/femsle/fnw040
[86] I. Y. Hwang, A. D. Nguyen, T. T. Nguyen, L. T. Nguyen, O. K.
Lee, E. Y. Lee, Appl. Microbiol. Biotechnol. 2018, 102 (7), 3071–
3080. DOI: https://doi.org/10.1007/s00253-018-8842-7
[87] Y. C. Jeon, A. D. Nguyen, E. Y. Lee, Catalysts 2019, 9 (11), 883.
DOI: https://doi.org/10.3390/catal9110883
[88] C. Cheng, T. Bao, S.-T. Yang, Appl. Microbiol. Biotechnol. 2019,
103 (14), 5549–5566. DOI: https://doi.org/10.1007/
s00253-019-09916-7
[89] Y. Shen, L. Jarboe, R. Brown, Z. Wen, Biotechnol. Adv. 2015,
33 (8), 1799–1813. DOI: https://doi.org/10.1016/
j.biotechadv.2015.10.006
[90] S.-H. Lee, E. J. Yun, J. Kim, S. J. Lee, Y. Um, K. H. Kim, Appl.
Microbiol. Biotechnol. 2016, 100 (19), 8255–8271. DOI: https://
doi.org/10.1007/s00253-016-7760-9
[91] F. R. Bengelsdorf, M. Straub, P. Dürre, Environ. Technol. 2013,
34 (13–14), 1639–1651. DOI: https://doi.org/10.1080/
09593330.2013.827747
[92] B. D. Heijstra, C. Leang, A. Juminaga, Microb. Cell Fact. 2017,
16 (1), 1–11. DOI: https://doi.org/10.1186/s12934-017-0676-y
[93] H. Latif, A. A. Zeidan, A. T. Nielsen, K. Zengler, Curr. Opin.
Biotechnol. 2014, 27, 79–87. DOI: https://doi.org/10.1016/
j.copbio.2013.12.001
[94] S. Dash, C. Y. Ng, C. D. Maranas, FEMS Microbiol. Lett. 2016,
363 (4). DOI: https://doi.org/10.1093/femsle/fnw004
[95] I. Y. Hwang et al., J. Microbiol. Biotechnol. 2014, 24 (12), 1597–
1605. DOI: https://doi.org/10.4014/jmb.1407.07070
www.cit-journal.com ª 2020 The Authors. Published by Wiley-VCH GmbH
Chemie
Review Ingenieur
Technik
[96] A. M. Henstra, J. Sipma, A. Rinzema, A. J. Stams, Curr. Opin. Bi-
otechnol. 2007, 18 (3), 200–206. DOI: https://doi.org/10.1016/
j.copbio.2007.03.008
[97] M. Diender, A. J. M. Stams, D. Z. Sousa, Front. Microbiol. 2015,
6, 1275. DOI: https://doi.org/10.3389/fmicb.2015.01275
[98] S. E. Lowe, M. K. Jain, G. J. Zeikus, Microbiol. Rev. 1993, 57 (2),
451–509.
[99] R. O. J. Norman, T. Millat, K. Winzer, N. P. Minton, C. Hodg-
man, Biochem. Soc. Trans. 2018, 46 (3), 523–535. DOI: https://
doi.org/10.1042/BST20170259
[100] F. T. Robb, S. M. Techtmann, F1000Research 2018, 7.
DOI: https://doi.org/10.12688/f1000research.16059.1
[101] J. Ferry, Life 2015, 5 (2), 1454–1471. DOI: https://doi.org/
10.3390/life5021454
[102] J. Bertsch, V. Müller, Biotechnol. Biofuels 2015, 8 (1), 1–12.
DOI: https://doi.org/10.1186/s13068-015-0393-x
[103] B. Molitor, E. Marcellin, L. T. Angenent, Curr. Opin. Chem. Biol.
2017, 41, 84–92. DOI: https://doi.org/10.1016/j.cbpa.2017.10.003
[104] C. R. Fischer, D. Klein-Marcuschamer, G. Stephanopoulos,
Metab. Eng. 2008, 10 (6), 295–304. DOI: https://doi.org/10.1016/
j.ymben.2008.06.009
[105] H. L. Drake, A. S. Gößner, S. L. Daniel, Ann. N. Y. Acad. Sci.
2008, 1125, 100–128. DOI: https://doi.org/10.1196/
annals.1419.016
[106] H. G. Wood, FASEB J. 1991, 5 (2), 156–163. DOI: https://doi.org/
10.1096/fasebj.5.2.1900793
[107] R. S. Hanson, T. E. Hanson, Microbiol. Rev. 1996, 60 (2),
439–471. DOI: https://doi.org/10.1128/mmbr.60.2.439-471.1996
[108] W. Van Hecke, R. Bockrath, H. De Wever, Bioresour. Technol.
2019, 293 (Sep), 122129. DOI: https://doi.org/10.1016/
j.biortech.2019.122129
[109] S. Y. Cheng, Y. Z. Liu, G. S. Qi, J. Mater. Sci. 2019, 54 (20),
13029–13044. DOI: https://doi.org/10.1007/s10853-019-03809-w
[110] J.-Z. Jiang, S. Zhang, X.-L. Fu, L. Liu, B.-M. Sun, Heat Mass
Transfer 2019, 55 (8), 2061–2072. DOI: https://doi.org/10.1007/
s00231-019-02580-7
[111] M. Köpke, C. Mihalcea, J. C. Bromley, S. D. Simpson, Curr. Opin.
Biotechnol. 2011, 22 (3), 320–325. DOI: https://doi.org/10.1016/
j.copbio.2011.01.005
[112] D. H. Hur, J.-G. Na, E. Y. Lee, J. Chem. Technol. Biotechnol.
2017, 92 (2), 311–318. DOI: https://doi.org/10.1002/jctb.5007
[113] K. Khosravi-Darani, Z. B. Mokhtari, T. Amai, K. Tanaka, Appl.
Microbiol. Biotechnol. 2013, 97 (4), 1407–1424. DOI: https://
doi.org/10.1007/s00253-012-4649-0
[114] P. J. Strong, B. Laycock, S. N. S. Mahamud, P. D. Jensen,
P. A. Lant, G. Tyson, S. Pratt, Microorganisms 2016, 4 (1).
DOI: https://doi.org/10.3390/microorganisms4010011
[115] C. E. Bjorck, P. D. Dobson, J. Pandhal, AIMS Bioeng. 2018, 5 (1),
1–38. DOI: https://doi.org/10.3934/bioeng.2018.1.1
[116] M. Øverland, A.-H. Tauson, K. Shearer, A. Skrede, Arch. Anim.
Nutr. 2010, 64 (3), 171–189. DOI: https://doi.org/10.1080/
17450391003691534
[117] N. Chu, Q. Liang, Y. Jiang, R. J. Zeng, Biosens. Bioelectron. 2020,
150, 111922. DOI: https://doi.org/10.1016/j.bios.2019.111922
[118] K. Asimakopoulos, H. N. Gavala, I. V. Skiadas, Chem. Eng. J.
2018, 348 (May), 732–744. DOI: https://doi.org/10.1016/
j.cej.2018.05.003
[119] I. K. Stoll, N. Boukis, J. Sauer, Chem. Ing. Tech. 2020, 92 (1–2),
125–136. DOI: https://doi.org/10.1002/cite.201900118
[120] M. Wu, Y. Wu, M. Wang, Biotechnol. Prog. 2006, 22 (4),
1012–1024. DOI: https://doi.org/10.1021/bp050371p
[121] R. C. Brown, Appl. Biochem. Biotechnol. 2007, 137–140 (1–12),
947–956. DOI: https://doi.org/10.1007/s12010-007-9110-y
Chem. Ing. Tech. 2020, 92, No. 11, 1665–1679
 Chemie
Ingenieur Review
Technik
[122] C. Weber, A. Farwick, F. Benisch, D. Brat, H. Dietz, T. Subtil,
E. Boles, Appl. Microbiol. Biotechnol. 2010, 87 (4), 1303–1315.
DOI: https://doi.org/10.1007/s00253-010-2707-z
[123] H. L. Drake, in Acetogenesis, Springer US, Boston, MA 1994.
[124] S. W. Ragsdale, E. Pierce, Biochim. Biophys. Acta, Proteins Proteo-
mics 2008, 1784 (12), 1873–1898. DOI: https://doi.org/10.1016/
j.bbapap.2008.08.012
[125] P. L. Tremblay, T. Zhang, S. A. Dar, C. Leang, D. R. Lovley, mBio
2012, 4 (1), e00406–12. DOI: https://doi.org/10.1128/
mBio.00406-12
[126] M. C. Schoelmerich, V. Müller, Proc. Natl. Acad. Sci. 2019,
116 (13), 6329–6334. DOI: https://doi.org/10.1073/
pnas.1818580116
[127] D. F. Emerson, G. Stephanopoulos, Curr. Opin. Biotechnol. 2019,
59, 39–45. DOI: https://doi.org/10.1016/j.copbio.2019.02.004
[128] C. Scott, Biology 2014, 3 (2), 255–263. DOI: https://doi.org/
10.3390/biology3020255
[129] J. L. Cotter, M. S. Chinn, A. M. Grunden, Enzyme Microb.
Technol. 2009, 44 (5), 281–288. DOI: https://doi.org/10.1016/
j.enzmictec.2008.11.002
[130] N. J. H. Averesch, F. Kracke, Front. Energy Res. 2018, 6 (Oct),
106. DOI: https://doi.org/10.3389/fenrg.2018.00106
[131] J. Helm, K.-D. Wendlandt, M. Jechorek, U. Stottmeister, J. Appl.
Microbiol. 2008, 105 (4), 1054–1061. DOI: https://doi.org/
10.1111/j.1365-2672.2008.03831.x
[132] www.nanalyze.com/2016/02/newlight-technologies-and-
aircarbon-plastic-from-air (accessed on September 07, 2020)
[133] www.unibio.dk/press-release-mitsubishi-corporation-invests-in-
and-partners-with-unibio/ (accessed on April 08, 2020)
[134] www.feedkind.com/ (accessed on April 01, 2020)
[135] www.stringbio.com/ (accessed on September 07, 2020)
[136] https://economictimes.indiatimes.com/small-biz/startups/
features/transforming-methane-gas-to-meat-equivalent-string-
bio-is-making-it-possible/articleshow/73079312.cms (accessed
on September 07, 2020)
[137] L. A. Alves, J. B. Almeida, E. Silva, M. Giulietti, J. Chem. Eng.
Data. 2007, 52 (6), 2166–2170. DOI: https://doi.org/10.1021/
je700177n
[138] R. Erbrecht, M. Felsch, H. König, W. Kricke, K. Martin, W. Pfeil,
R. Winter, W. Wörstenfeld, Das Große Tafelwerk Interaktiv,
Cornelsen, Berlin 2006.
[139] L. H. Geventman, in CRC Handbook of Chemistry and Physics
(Ed: D. R. Lide), 81st ed., CRC Press, Boca Raton, FL 1999.
[140] M. Losen, B. Frolich, M. Pohl, J. Buchs, Biotechnol. Prog. 2004,
20 (4), 1062–1068. DOI: https://doi.org/10.1021/bp034282t
[141] A. Knoll, B. Maier, H. Tscherrig, J. Büchs, Adv. Biochem. Eng.
Biotechnol. 2005, 92, 77–99. DOI: https://doi.org/10.1007/
b98918
[142] F. Garcia-Ochoa, E. Gomez, Biotechnol. Adv. 2008, 27 (2),
153–176. DOI: https://doi.org/10.1016/j.biotechadv.2008.10.006
[143] I. Knabben, L. Regestein, F. Marquering, S. Steinbusch, A. R.
Lara, J. Büchs, J. Biotechnol. 2010, 150 (1), 73–79. DOI: https://
doi.org/10.1016/j.jbiotec.2010.07.006
[144] K. M. Hurst, R. S. Lewis, Biochem. Eng. J. 2010, 48 (2), 159–165.
DOI: https://doi.org/10.1016/j.bej.2009.09.004
[145] J. Jack, J. Lo, P. C. Maness, Z. J. Ren, Biomass Bioenergy 2019,
124 (March), 95–101. DOI: https://doi.org/10.1016/
j.biombioe.2019.03.011
[146] N. Jand, M. Yasin, S. Park, R. W. Lovitt, I. S. Chang, Bioresour.
Technol. 2017, 102–108. DOI: https://doi.org/10.1016/
j.ab.2018.02.027
[147] T. Zhang, J. Zhou, X. Wang, Y. Zhang, Iran. J. Biotechnol. 2019,
17 (1), 10–16. DOI: https://doi.org/10.21859/ijb.1866
Chem. Ing. Tech. 2020, 92, No. 11, 1665–1679 ª 2020 The Authors. Published by Wiley-VCH GmbH
1679
[148] A. Infantes, M. Zwick, I. K. Stoll, N. Boukis, F. Oswald, A. Neu-
mann, Chem. Ing. Tech. 2018, 90 (9), 1283–1284. DOI: https://
doi.org/10.1002/cite.201855330
[149] F. Oswald, I. K. Stoll, M. Zwick, S. Herbig, J. Sauer, N. Boukis,
A. Neumann, Front. Bioeng. Biotechnol. 2018, 6 (Feb).
DOI: https://doi.org/10.3389/fbioe.2018.00006
[150] J. Schwarz-Linek, K.-D. Wendlandt, M. Jechorek, U. Stottmeister,
J. Appl. Microbiol. 2008, 105 (4), 1054–1061. DOI: https://
doi.org/10.1111/j.1365-2672.2008.03831.x
[151] I. K. Stoll, N. Boukis, J. Sauer, in Proc. of the 27th European Bio-
mass Conference and Exhibition 2019, 1255–1261. DOI: https://
doi.org/10.5071/27theubce2019-3cv.3.4
[152] M. Can, F. A. Armstrong, S. W. Ragsdale, Chem. Rev. 2014,
114 (8), 4149–4174. DOI: https://doi.org/10.1021/cr400461p
[153] S. Ramió-Pujol, R. Ganigué, L. Bañeras, J. Colprim, FEMS Micro-
biol. Lett. 2018, 365 (10), 10–13. DOI: https://doi.org/10.1093/
femsle/fny084
[154] S. Menon, S. W. Ragsdale, Biochemistry 1996, 35 (49), 15814–
15821. DOI: https://doi.org/10.1021/bi9615598
[155] M. D. Bredwell, P. Srivastava, R. M. Worden, Biotechnol. Prog.
1999, 15 (5), 834–844. DOI: https://doi.org/10.1021/bp990108m
[156] Y. K. Kim, S. E. Park, H. Lee, J. Y. Yun, Bioresour. Technol. 2014,
159, 446–450. DOI: https://doi.org/10.1016/j.bio-
rtech.2014.03.046
[157] www.mt.com/int/en/home/products/Process-Analytics/DO-
CO2-ozone-sensor/dissolved-carbon-dioxide.html (accessed on
March 30, 2020)
[158] J. R. Phillips, H. K. Atiyeh, R. S. Tanner, J. R. Torres, J. Saxena,
M. R. Wilkins, R. L. Huhnke, Bioresour. Technol. 2015, 190,
114–121. DOI: https://doi.org/10.1016/j.biortech.2015.04.043
[159] I. Schlembach, L. Regestein, M. A. Rosenbaum, BioSpektrum
2017, 23 (3), 270–272. DOI: https://doi.org/10.1007/
s12268-017-0794-4
[160] H. Richter, B. Molitor, M. Diender, D. Z. Sousa, L. T. Angenent,
Front. Microbiol. 2016, 7 (Nov). DOI: https://doi.org/10.3389/
fmicb.2016.01773
[161] H. Richter, M. E. Martin, L. T. Angenent, Energies 2013, 6 (8),
3987–4000. DOI: https://doi.org/10.3390/en6083987
[162] B. Molitor, A. Mishra, L. T. Angenent, Energy Environ. Sci. 2019,
12 (12), 3515–3521. DOI: https://doi.org/10.1039/c9ee02381j
[163] F. Oswald, S. Dörsam, N. Veith, M. Zwick, A. Neumann, K. Och-
senreither, C. Syldatk, Front. Microbiol. 2016, 7 (Jun), 1–12.
DOI: https://doi.org/10.3389/fmicb.2016.00891
[164] M. Mann, G. Munch, L. Regestein, L. Rehmann, ACS Sustainable
Chem. Eng. 2020, 8 (7), 2632–2639. DOI: https://doi.org/
10.1021/acssuschemeng.9b05439
[165] J. O. Park et al., Nat. Metab. 2019, 1 (6), 643–651. DOI: https://
doi.org/10.1038/s42255-019-0077-0
[166] B. T. Maru, P. C. Munasinghe, H. Gilary, S. W. Jones, B. P. Tracy,
FEMS Microbiol. Lett. 2018, 365 (8), 1–8. DOI: https://doi.org/
10.1093/femsle/fny039
[167] A. G. Fast, E. D. Schmidt, S. W. Jones, B. P. Tracy, Curr. Opin.
Biotechnol. 2015, 33, 60–72. DOI: https://doi.org/10.1016/
j.copbio.2014.11.014
[168] K. Tabata, I. Okura, J. Japan Pet. Inst. 2008, 51 (5), 255–263.
DOI: https://doi.org/10.1627/jpi.51.255
[169] J. S. Han, C. M. Ahn, B. Mahanty, C. G. Kim, Appl. Biochem. Bio-
technol. 2013, 171 (6), 1487–1499. DOI: https://doi.org/10.1007/
s12010-013-0410-0
[170] J. Schrader, M. Schilling, D. Holtmann, D. Sell, M. V. Filho,
A. Marx, J. A. Vorholt, Trends Biotechnol. 2009, 27 (2), 107–115.
DOI: https://doi.org/10.1016/j.tibtech.2008.10.009
www.cit-journal.com