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Journal Pre-Proof: Biotechnology Advances
Journal Pre-Proof: Biotechnology Advances
PII: S0734-9750(19)30200-9
DOI: https://doi.org/10.1016/j.biotechadv.2019.107500
Reference: JBA 107500
Please cite this article as: X. Qian, L. Chen, Y. Sui, et al., Biotechnological potential
and applications of microbial consortia, Biotechnology Advances (2019), https://doi.org/
10.1016/j.biotechadv.2019.107500
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Xiujuan Qiana, Lin Chena, Yuan Suib, Chong Chenb, Wenming Zhanga,c, Jie Zhoua,c,
a
State Key Laboratory of Materials-Oriented Chemical Engineering,
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College of Biotechnology and Pharmaceutical Engineering,
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Nanjing Tech University, Nanjing, China
b pr
2011 College, Nanjing Tech University, Nanjing, China
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c
Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM),
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d
Institute of Process Engineering in Life Sciences, Section II: Technical Biology,
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Tel/Fax: 0086-25-58139927
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Abstract
in turn offers insights into the optimal design of synthetic microbial consortia. Yet, the
study of synthetic microbial consortia is still in early infancy, facing many unknowns
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and challenges in intercellular communication and construction of stable and
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controllable microbial consortia systems. In this review, we comprehensively
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discussed the recent application of defined microbial consortia in the fields of human
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health monitoring and medicine exploitation, valuable compounds synthesis,
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Introduction
opportunities for the production of bulk chemicals and valuable products (Hall and
Howe, 2012). However, the inherent exclusiveness to foreign genes, the lack of novel
enzymes, the existence of silent pathways and requirements for rigid cultivation
conditions always affect bio-product titer and productivity (Bhatia et al. , 2018, Shong
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(Gustavsson and Lee, 2016), leaving the question of whether the traditional metabolic
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strategy, i.e. construction of “super cell factories” is sufficient for sustainable
biorefineries. pr
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Nevertheless, traditional food fermentation processes, such as cheese and soy
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sauce production are typically carried out by using mixed cultures consisting of
multiple strains or species (Hanemaaijer et al. , 2015). Moreover, more than 99% of
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expected, more and more studies related to the exploration of microbial consortia
microbial consortia systems have been reported recently (Fig. 1) (An et al. , 2019,
Roell et al. , 2019, Song et al. , 2014, Wang et al. , 2019b, Zhang and Wang, 2016).
in the activation of silent metabolic pathways, which are not expressed under “normal”
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human health, as humans are co-evolving with trillions of microbes that inhabit in our
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bodies, which created complex, body-habitat-specific and adaptive ecosystems to
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adapt to the relentlessly changing host physiology (Turnbaugh et al. , 2007). Second,
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microbial consortia employ the approach of “division of labor”, allowing a burden
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distribution across the population and permitting improved efficiency and more
complex behavior than monocultures (Hays et al. , 2015, Zhou et al. , 2015). It might
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binding sites, terminators, and vectors, etc. are needed when using monocultures
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(Roell et al. , 2019). Third, such microbial communities consist of multiple functional
Ledesma-Amaro, 2018).
In this review, recent applications using artificial microbial consortia in the area
highlighted.
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health supervision
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The serendipitous discovery of penicillin using microbial consortia of Penicillium
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and Staphylococcus by Alexander Fleming in 1929 was regarded as one of the most
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influential scientific breakthroughs in last century (Bennett and Chung, 2001). Since
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then, more and more novel chemicals have been discovered especially with the
using microbial consortia reported in the last decade. As seen, most of them exhibit
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antimicrobial properties and can only be found in microbial consortia systems. Due to
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the increasing number of pathogenic antibiotic-resistant strains, the need for research
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and development of new antibiotic substances is more relevant than ever (Tacconelli
et al. , 2018). The unique characteristic of microbial consortia clearly highlights its
The growing number of available microbial genome sequences showed that many
are presumably silent under standard laboratory conditions (Marmann et al. , 2014),
e.g. the silent glycopeptide cluster in Amycolatopsis (Spohn et al. , 2014). There is
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evidence that the activation of some silent gene clusters requires the physical presence
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compounds, such as N-acyl homoserine lactones (AHLs) and small peptides, to
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perform as transcriptional regulators and epigenetic modifiers in a process called
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“quorum sensing” (QS) (Joint et al. , 2002). AHLs are major class of autoinducer
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signal molecules used by gram-negative bacteria for intraspecies QS (Ng and Bassler,
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2009). Once AHL concentration in the environment reaches a threshold level, they
will activate the transcriptional regulator proteins of LuxR family. The LuxR/AHL
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complex can activate the expression of multiple target genes, including those required
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for AHL synthesis (Joint et al. , 2002) (Fig. 2a). Such QS mechanism has been
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Escherichia coli (Basu et al. , 2004), to control the population in microbial consortia
by regulating cell growth and death (Balagaddé et al. , 2008, You et al. , 2004), and to
reduce the substrate competition between different species (Wang et al. , 2019a). In
(AIPs) are mostly used as QS molecules (Ng and Bassler, 2009, Thoendel and
Horswill, 2010). Different from AHLs, these peptides vary in sequence and structure,
which are actively exported from the cell by dedicated transporters (Michie et al. ,
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DNA-binding response regulator (Fig. 2b). Once the critical concentration of AIP is
and imported into the cell. The phosphorylated AIP will bind on the target DNA to
regulate its transcription (Michie et al. , 2016). Beyond the chemical communication
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in the same genus consortia, QS molecules also seem to influence
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prokaryote-eukaryote interactions. For example, orsellinic acid derivatives are usually
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found in a fungal/bacterial mutualism, implying the functional role of orsellinic acid
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in microbial communication (Brakhage and Schroeckh, 2011, Fischer et al. , 2018,
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transport of some signal molecules also needs to be assisted by a special structure. For
example, hydrophobic signals such as long-chain AHLs are transported between cells
by membrane vesicles (MVs) (Toyofuku, 2019) (Fig. 2c). In some cases, an intimate
physical contact of the cell members within a consortium is required to elicit the
specific communication. The classical case was the interaction between Aspergillus
Further gene level analysis indicated that microbial consortia cause a series of
gene expression changes in the manner of gene loss, histone modification, and
clavuligerus with Staphylococcus aureus N315 led to the loss of a large 1.8 Mbp
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clavuligerus acquired the ability to constitutively produce holomycin within this
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microbial consortia system (Charusanti et al. , 2012). Speculatively, the loss of gene
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segment in S. clavuligerus may reduce the metabolic burden during replication and
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gene expression. In return, the silent holomycin synthetic pathway was specifically
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activated, which is a member of the pyrrhotine class of antibiotics and shows great
cytotoxicity levels against S. aureus (Oliva et al. , 2001). Bacterium could also alter
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fungal gene expression by inducing histone modification through the main histone
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Moreover, genomic analysis revealed that Rhodococcus 307CO harbors a large DNA
segment derived from Streptomyces within the microbial consortia system, leading to
and lead to the incorporation of prey DNA by predator (Pérez et al. , 2011).
microfluidic technique and flow cytometry, cell isolation and printing, and
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high-throughput cultivation should be developed.
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In addition to the antibiotic chemicals discovery, microbial consortia also play
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promising roles in clinical research. Microorganisms that colonize the human body,
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including mucosal and skin environments are at least as abundant as our somatic cells
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and certainly contain far more genes than our human genome (Gilbert et al. , 2018,
addition to genetics and environment that influence human health (Turnbaugh et al. ,
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2007). For example, the gut microbiome is now emerging as an important player in
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polysaccharides, and is essential for the development and homeostasis of the immune
system in the gut to resist against pathogenic bacteria (Chen et al. , 2018). An
elaboration of the exact mechanism of such communities has also become a priority in
and Saccharomyces cerevisiae for high value product synthesis. Usually, these
products can only be synthesized through long or complex metabolic pathways. For
example, 35 to 51 steps were required for taxol de novo synthesis from glucose.
Modification of metabolic pathway in E. coli gave the highest taxadiene titer of 1.02
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g/L, which is the precursor of taxol (Ajikumar et al. , 2010). However, the process
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was still far from industrial manufacturing. In another study, a biosynthetic pathway
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containing 10 genes for the synthesis of dihydrosanguinarine and sanguinarine from
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(R, S)-norlaudanosoline was constructed in S. cerevisiae (Fossati et al. , 2014). This
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multiple genes are simultaneously introduced into a single microorganism, as this will
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potentially overcome through rational design using microbial consortia, which could
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modularize and segregate one biosynthetic pathway into multiple separate cells.
consortia systems, E. coli was the most commonly used chassis. Zhang et al. (2015b)
designed a novel E. coli-E. coli co-culture for the production of cis, cis-muconic acid
(MA) and 4-hydroxybenzoic acid (4HB), which both are important platform
muconic acid and vanillyl alcohol (Sengupta et al. , 2015, Wang et al. , 2018b). In this
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study, a first E. coli was used for conversion of glucose into the intermediate
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3-dehydroshikimic acid (DHS), which was assimilated and subsequently converted to
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MA or 4HB by the second E. coli strain. To eliminate carbon source competition
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between these two strains, the phosphotransferase system in the first strain was
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removed, and the xylose isomerase gene xylA, which catalyzes the inter-conversion of
D-xylose and D-xylulose, was deleted in the second strain. The resulting consortium
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could consume xylose and glucose simultaneously. By using this strategy, the
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utilization were successfully overcome. This principle has also been used for the
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of glucose and glycerol (Wang et al. , 2018a), and the production of glycosides from a
accommodating the upstream and downstream pathways into two independent E. coli
strains, Zhang et al. constructed a microbial consortia system, in which glycerol was
used as the sole carbon source to support the growth of both strains as well as MA
production. The E. coli-E. coli co-culture can be used for complex biosynthesis
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pathway engineering in the context of sole carbon source, regardless of the growth
coli co-cultures. Using this approach, the pyranoanthocyanins production are more
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stable than the traditional extraction method from plants. Moreover, synthetic E.coli
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consortia systems have been designed for more and more valuable compounds
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production, including ester compounds like caffeoylmalic acid (Li et al. , 2018),
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terpene compounds like α-pinene (Niu et al. , 2018), polyphenol compounds like
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2018b), amino acid derivative like 3-amino-benzoic acid (3AB) (Zhang and
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2-O-b-D-glucoside (Ahmadi et al. , 2016), and monolignols (Chen et al. , 2017) etc. In
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2016).
modules of monacolin J and its derivative lovastatin, a very important natural product
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be assembled into two Pichia pastoris strains. The microbial consortia cangenerate
250.8 mg/L of lovastatin and 593.9 mg/L of monacolin J from methanol (Liu et al. ,
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between bacteria and eukaryotes have also been developed for biosynthesis of
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complex valuable products. For example, Rodríguez-Bustamante et al. (2005) isolated
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a microbial consortium consisting of the yeast Trichosporon asahii and the bacterium
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Paenibacillus amylolyticus, where T. asahii was responsible for cleaving lutein to
glucose as the sole carbon source, although neither of them can produce the paclitaxel
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precursor (Zhou et al. , 2015). In this process, the engineered E. coli strain was
responsible for upstream de novo biosynthesis of taxadiene, which was then converted
inhibited the growth of E. coli and the production of taxanes. Hence, to better control
the population allocation of these two strains, a mutualistic carbon-source method was
employed, where xylose was consumed and converted to acetate by E. coli, and then
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coli and S. cerevisiae for improving the efficiency of naringenin production, which is
a value-added natural product and widely dispersed in the citrus plant of rutaceae
family. Specifically, the endogenous tyrosine pathway was introduced into E. coli for
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high level production of tyrosine, which was subsequently converted into naringenin
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by a downstream engineered S. cerevisiae. As a result, 21.16 mg/L of naringenin was
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finally produced from xylose, showing an 8-fold increased titer compared to that of
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yeast monoculture. Such systems have also been designed to exchange tyrosine and
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three or more strains were also successfully exploited for constructing a long tandem
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coli, Bacillus subtilis and Shewanella oneidensis has been designed for microbial
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power generation (Liu et al. , 2017). In this process, E. coli firstly digested glucose to
produce lactate, which was used as carbon source and electron donor. Subsequently,
oxidized lactate to produce acetate, which served as carbon source for E. coli and B.
which performed “better together” for energy generation. Under optimized condition,
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than 15 days. The potential of modular co-culture engineering can address the
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improvement in rosmarinic acid production compared to that of the mono-culture (Li
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et al. , 2019). Another polyculture example was the de novo synthesis of anthocyanin,
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an important health-promoting pigment (Jaakola, 2013). In this study, 15 enzymatic
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steps involved in the production of phenylpropanoic acids, flavanones, flavan-3-ols,
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realizing the first heterologous production of flavan-3-ols (Jones et al. , 2017). This
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study represents the most complex synthetic consortia to date, providing a new
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industrial applications using such multispecies cultures . Except for the modular strain
will cause the production of some secondary chemicals, which brings more
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induced secondary chemicals will affect the natural chemicals quality should be taken
into account; ②In contrast to single cell factories, each species within microbial
consortia will interact with each other through the interchange of substrates or
transfer between cells is the key to construct a highly efficient microbial consortium.
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In addition, the low concentration of some intermediate metabolites will bring
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difficulties for partner microorganism to sense and capture them efficiently. Therefore,
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some versatile fermentation equipments should be designed to enhance the substrates
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or intermediates transfer within a microbial consortium system; ③ Microbial
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stability (Roell et al. , 2019). Thus, it is premature to judge the potential of a microbial
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production process, more attention should be paid to these aspects in later experiment
design.
consortia
2012). Nevertheless, separating these tasks will cause inevitably high costs and long
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production of lignocellulose degrading enzymes, lignocellulose hydrolysis and
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microbial fermentation in one step has been considered as an economical and efficient
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approach to produce desired products from polysaccharides (Olson et al. , 2012, Xin
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et al. , 2017). Previous CBP reviews addressed fermentative production of chemicals
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with recombinant lignocellulosic microbes (Fig. 3a) (Jang et al. , 2012, Yang et al. ,
non-lignocellulosic microbes (Fig. 3b) (Edwards et al. , 2011, Favaro et al. , 2015,
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challenge due to the assembly of differential models into a single synthetic chassis
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with the capability to produce all desired lignocellulose degrading enzymes (van Zyl
in current CBP microorganisms remained at only several hundred filter paper unit
(FPU)/L (den Haan et al. , 2015, Guo et al. , 2018, Singh et al. , 2018), which were
notably lower than that from native cellulolytic fungi, e.g. Trichoderma reesei, a
wild-type T. reesei and wild-type Lactobacilli sp. were co-cultivated, 19.8 g/L of
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lactic acid corresponding to 85.2% of the theoretical maximum yield was obtained
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from non-detoxified steam-pretreated beech wood (Shahab et al. , 2018). Buzzini et al.
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designed a microbial co-culture of wild-type Debaryomyces castellii and wild-type
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Rhodotorula glutinis for the production of carotenoids from oligosaccharides and
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dextrins from corn syrup. D. castellii was applied to hydrolyze the raw substrate to
Finally, 8.2 mg/L of carotenoid was produced from corn syrup in the fed-batch
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switchgrass, corn stover, sugar cane bagasse and poplar (Bayer et al. , 2009).
mutualism consortium, which realized the production of L-lysine and its derivatives
source. The generated glucose from starch by E. coli was then used to feed C.
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facilitate its growth. The mutualism of each species guaranteed the stable cooperation
Particularly, the major contribution of microbial consortia CBP was applied for
bioenergy production, such as bioethanol, biobutanol, microbial lipid and H2 (Table 3).
For bioethanol production, Patle and Lal demonstrated that a microbial community of
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Zymomonas mobilis and Candida tropicalis could transform enzymatically
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hydrolyzed lignocellulosic biomass into ethanol with a high yield of 97.7% (Patle and
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Lal, 2007). A polyculture of T. reesei, S. cerevisiae and Scheffersomyces stipitis could
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achieve cellulolytic enzyme production, hexose conversion and pentose sugar
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utilization in one pot, realizing ethanol de novo synthesis from slurry dilute acid
pretreated wheat straw without detoxification (Brethauer and Studer, 2014). Similarly,
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more microbial consortia CBP systems for bioethanol, biobutanol and isobutanol
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been designed (Minty et al. , 2013, Patle and Lal, 2007, Suriyachai et al. , 2013,
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pretreated wheat straw, resulting in 23.3 g/L of total ABE with 3.7 g/L of ethanol, 14.2
g/L of butanol and 5.4 g/L of acetone (Valdez-Vazquez et al. , 2015). In parallel, Wen
solvents production from alkali extracted deshelled corn cobs (AECC). Under
optimized conditions, the microbial consortium degraded 68.6 g/L of AECC and
produced 11.8 g/L of solvents (2.6 g/L of acetone, 8.3 g/L of butanol, and 0.9 g/L of
ethanol) in less than 80 h, with 17.2% solvents conversion rate. Further genetic
modification of this consortium improved the solvent production to 22.1 g/L from
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83.2 g/L of lignocellulose hydrolysate, and AECC degradation was increased by
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21.3%, while solvents titer was enhanced by 87.2% (Wen et al. , 2017). In terms of
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microbial lipid production, Papone et al. (2016) reported a co-culture of microalgae
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Chlorella sp. KKU-S2 and yeast Toluraspora globosa YU5/2. A maximum biomass
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concentration of 6.90 g/L with a lipid concentration of 0.33 g/L was obtained using
systems over pure monocultures, many attempts have also been made in biogas and
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biohydrogen production (Ike et al. , 1999, Laxman Pachapur et al. , 2015, Masset et
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al. , 2012).
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Generally, substrate degradation efficiency is still the rate limiting step in CBP.
microbial strain can not efficiently secrete all desirable components of lignocellulose
cellulases and hemicellulases complex (Kumar et al. , 2008). For example, high
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for A. oryzae in combination with other fungi, in particular with P. chrysosporium (Hu
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et al. , 2011). The overall activity of degrading enzyme in the microbial consortia is
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not the sole sum of activities of individual microorganism species, which in some
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cases exceeded the sum of single incubations.Co-cultivation of these lignocellulose
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degrading consortia with biological detoxification species could further improve the =
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the ecosystem, such as water quality deterioration, heavy metals pollution and loss of
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2019, Critchell et al. , 2019, Ibrahim et al. , 2016, Walker et al. , 2019). To achieve
environmental pollutants using single strains is still very low and restricted (Villegas
et al. , 2014). Therefore, more and more attention has been shifted towards microbial
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consortia, since their inherent multiple function, robust and adaptable characteristics.
elements such as nitrogen (N), phosphorus (P), pollutants and toxins (Mujtaba and
denitrification steps, however, several cycles of these three steps are required to
achieve the EU legislation accepted nutrient levels, and each step requires several
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tanks and internal recycles of activated sludge, resulting in an overall increase of
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process cost, complexity and energy input (Gonçalves et al. , 2017). Comparatively,
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microalgal consortia (microalgae and bacteria/fungi) provide an efficient approach for
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water remediation. For instance, co-culture of microalgae Scenedesmus dimorphus
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and nitrifiers enhanced the removal of N and P from wastewater by 3.4 and 6.5 times,
microalga Chlorella vulgaris and bacterium P. putida also showed higher removal
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efficiency of both nutrients (N and P) and chemical oxygen demand (COD) than each
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anaerobic sludge, 89% N removal and 80% P removal from starch wastewater were
achieved (Ren et al. , 2015). In the view of symbiotic relationship, microalgae can
CO2 and growth promoting factors for microalgae, such as vitamins and siderophores
(Fig. 4) (Abinandan et al. , 2018, Bordel et al. , 2009). In addition, microalgae can
also serve as refuge for bacteria, protecting them from hostile environmental
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conditions (Byappanahalli et al. , 2009, Mandal et al. , 2011, Unnithan et al. , 2014).
(Bhatia et al. , 2017, Wrede et al. , 2014), and animal feed preparation (Stiles et al. ,
2018), which further improving process economy. Despite the obvious advantages of
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intensities and appropriate temperature still seriously limits its scale-up progress in
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wastewater treatment (Osundeko et al. , 2019). In addition, the recovery and
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processing of microalgae from the cultivation medium are still a challenge, since
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needs a high energy input is needed (Osundeko et al. , 2019). More functional facility
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Heavy metals, such as zinc and nickel are considered as the most hazardous
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pollutants, because they can affect the structure of nucleic acids and proteins.
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Shafique et al. , 2017), the metal removal capability using monoculture is still
able to absorb a mixture of Zn(II) and Ni(II) ions (Kipigroch et al. , 2012). Ilamathi et
aeruginosa, B. subtilis and E. coli in a liquid-solid fluidized bed for heavy metal
Azo dyes, the largest chemical class of dyes with the greatest variety of colors are
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commonly released from textile, dyestuff and dyeing industry, which cause serious
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environmental pollution because of their color, biorecalcitrance and potential toxicity
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to animal and human (Senan and Abraham, 2004). Nevertheless, it is very difficult to
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decolorize these dyes by common physical and chemical methods (Khan et al. , 2013).
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Microbial strains are able to decolorize azo dyes, but the degradation products are
frequently toxic aromatic amines or metabolites that are even more difficult to
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degrade than the parent dye (Solís et al. , 2012). Microbial consortia treatment
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systems could achieve a higher degree of biodegradation and mineralization due to the
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et al. , 2009). The decolorization of sulfonated reactive dye Green HE4BD using
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than that using the individual microorganisms (Saratale et al. , 2010). In these
microbial consortia, individual strains may attack the dye molecule at different
positions or even utilize resulting degradation products, such as the toxic aromatic
amines produced by partner strains for further decomposition (Saratale et al. , 2011).
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pollutants, like pesticides, antibiotics and other toxins. For example, co-culture of
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Pseudomonas and Staphylococcus was shown to be more efficient in removing phenol
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than their monocultures (Senthilvelan et al. , 2014). Co-culture of Serratia and
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Trichosporon sp. could completely mineralize chlorpyrifos, one of the most widely
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Klebsiella pneumoniae and Ralstonia sp. showed better tolerance to thiocyanate with
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a degradation rate of 500 mg/L/d. Poly-culture of Arthrobacter sp. NB1, Serratia sp.
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nitrobenzene compared with monoculture (Jin et al. , 2012). Moreover, other studies
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al. , 2011).
Future perspectives
energy and environment, etc. has prompted the rapid development of biotechnology.
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more complex chemicals, which only exist in plants and can not be synthesized by
accomplish this complex task through the division of labor. However, these synthetic
microbial consortia are still relatively simple, in which usually two or three wild type
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of synthetic microbial consortia is still maintained at trial stage and lack of theory
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guide, as microorganisms assembly seems random. To construct a more robust, stable
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and controllable microbial consortium, several challenges must be addressed.
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Stable coexistence of different species within one microbial consortium is
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commonly used one, in which growth conditions were adjusted based on different
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strains (Shahab, 2019). However, this would lead to longer fermentation duration and
microcapsule and microfluidic laminar flow techniques can help create a relatively
optimal microenvironment for individual cells, and the mechanical separation of each
microbial species would not affect microbial growth in a complex microbial consortia
system (Wang et al. , 2019, Lindemann et al. , 2016). And also, bioreactor equipped
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with some inlets, on which parceled with gas permeable dense membranes or other
which could meet the requirement for different nutrient of microbial consortia
A rational population structure and substrates allocation modes are another two
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inoculum size and time of different species within microbial consortia is the most
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direct and efficient way to adjust the population structure. However, the substrate
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competition may exist if each species was fed by the same carbon source, and this
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would lead to the uncontrollable growth of each species within microbial consortia.
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can specifically utilize different carbon sources, and this would efficiently reduce the
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growth competition. For instance, pentose and hexose utilization pathways can be
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metabolically constructed in different species (Zhang et al. , 2015b). This would not
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only eliminate the substrate competition, but also achieve simultaneous utilization of
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first strain. Then partner strain, which lost the utilization capability of
2015). The ratio of these two species could be balanced by the substrate and
member, growth related genes could be regulated at different levels to further adjust
Efficient mass transfer, including the intermediates, energy and cofactors can
improve the product efficiency by using microbial consortia. In contrast to single cell
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factories, intermediates have to be delivered to other partner strains. The complex
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metabolic pathways within all species of microbial consortia made the metabolic
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regulation more difficult. Herein, a spatial organization concept, or named
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3-dimensional (3D) began to show up. In a 3D consortium, microorganisms are
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lower fitness, enhance the efficient metabolite and signal molecule transfer among
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(Agapakis et al. , 2012, Johns et al. , 2016). In fact, such 3D microbial consortia
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widely exist in natural environment. A typical example is the anaerobic sludge granule,
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wrap outside of granules to break down complex organic molecules into acids, which
(MacLeod et al. , 1990). This spatial organization creates optimal growth environment
for different species of microorganisms in these three layers, and realizes efficient
Chlamydomonas reinhardtii (Das et al. , 2016). Within this system, A. aceti produced
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cellulose and acetate mats at the air-water interface when growing in liquid cultures.
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Consequently, C. reinhardtii thrived in an acetate-rich medium and produced oxygen
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for A. aceti. By co-cultivating these two microorganisms, researchers created a
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composite material using cellulose produced in situ by Acetobacter, which offered a
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matrix to favor the cell growth and entrap microalgae cells (Das et al. , 2016). Another
in which cells can share nutrients and are sheltered from harmful factors in the
have been developed recently (Wondraczek et al. , 2019). For example, microfluidic
and microwell devices have been used to help building microbial communities, where
exchange freely (Kim et al. , 2008). Strategies using inkjet printing cells and
arranged in defined geometric patterns, which has been used for microbial
communities construction with more complex structures (Connell et al. , 2013, Hays
et al. , 2015). Moreover, fiber structure like calcium alginate fibers with one species in
the core and another in the exterior can also realize strains ordered arrangement with a
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complex consortium system (Kim et al. , 2010). With the increasing understanding of
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systems biology and metabolic dynamics in various microbial consortia, more
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biocompatible and functionalized supporting materials for organizing microbial
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consortia will be developed in the future.
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developed (Jones et al. , 2016, Klitgord and Segre, 2010, Lindemann et al. , 2016,
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Manikandan and Viruthagiri, 2010, Panda et al. , 2010, Park et al., 2011, Sun et al. ,
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2010, Suriyachai et al. , 2013). For this purpose, Minty et al. (2013) have designed an
symbiotic consortium of E. coli and T. reesei. The sophisticated model allowed the
development of computational tools can also help elaborate the interaction mechanism
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(Stams and Plugge, 2009), the inner life of sludge (Liu et al. , 2002), soil and
rhizosphere ecosystems (Kent and Triplett, 2002), and marine environment (Ka and
Keerthi, 2017), which will further provide theoretical guidance for construction of
Conclusion
f
Synthetic microbial consortia possess several promising characteristics and
oo
potential over monocultures, which harness the resources and metabolic power of
pr
multiple microbial strains to meet the requirements of discovery of novel chemicals
e-
and functional reconstitution of complex pathways. More importantly, microbial
Pr
consortia offer a viable option to share the undesired metabolic burden among
different microbial strains and go beyond the limit of the metabolic capacity within a
al
single microbial strain. And it also presents a new approach for efficient utilization of
rn
of analytical and predictable computational models should be carried out in the future.
will be rationally designed for many intriguing applications in the foreseeable future.
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Acknowledgements
This work was supported by National Key Research and Development Program
f
Biomass-based Green Fuels and Chemicals Foundation (JSBEM201908), and Project
oo
of State Key Laboratory of Materials-Oriented Chemical Engineering (ZK201601).
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- p
Antibacterial and No (Rateb et al. , 2013)
e
S. bullii alkaloids antiprotozoal
Fusarium tricinctum &
Fusarium begoniae
Subenniatins A and B
al
Trichophyton rubrum & 4″-hydroxysulfoxy-2,2″ N/A No (Bertrand et al. ,
rn
Bionectria ochroleuca -dimethylthielavin P 2014)
Aspergillus nidulans & Orsellinic acid, lecanoric acid N/A No (Schroeckh et al. ,
Collection of 58 actinomycetes
o u
F-9775A, F-9775B (1) (1) Cathepsin K inhibitors 2009)
Streptomyces clavuligerus &
Staphylococcus aureus
Salinispora arenicola &
J
Holomycin (2)
Emericellamides A and B
(2) Antimicrobial activity
Antibacterial activities
No
Yes
(Charusanti et al. ,
2012)
(Oh et al. , 2007)
Emericella sp.
Penicillium pinophilum & Secopenicillide C N/A No (Nonaka et al. , 2011)
Trichoderma harzianum Penicillide, MC-141 and Yes
Stromemycin
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n a
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Table 2. Summary of recent progress in valuable compound production applying modular co-culture engineering.
Improvement compared to
Co-culture Product Reference
monoculture/other method*
E. coli-E. coli
4-hydroxybenzoic acid
(4HB)
- p
8.6-fold titer improvement (Zhang et al. , 2015b)
E. coli-E. coli
3-hydroxybenzoic acid
r e
5.3-fold titer improvement (Zhou et al. , 2019)
P
(3HB)
rn
production and productivity
E. coli-E. coli Apigetrin 2.1-fold titer improvement (Thuan et al. , 2018a)
E. coli-E. coli
o u
Caffeoylmalic acid 5-fold titer improvement (Li et al. , 2018)
E. coli-E. coli
E. coli-E. coli
J Salidroside
Resveratrol glucosides
Over 20-fold titer improvement
2.9-fold titer improvement
(Liu et al. , 2018a)
(Thuan et al. , 2018b)
E. coli-E. coli Naringenin 1.5-fold titer improvemen (Ganesan et al. , 2017)
Bisdemethoxycurcumin 6.28 mg/L in titer, BDMC first de novo
E. coli-E. coli (Fang et al. , 2018)
(BDMC) production from glucose*
E. coli-E. coli Caffeyl alcohol 12-fold improvement (Chen et al. , 2017)
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E. coli-E. coli Muconic acid (MA) 14-fold titer improvement (Zhang et al. , 2015a)
3-amino-benzoic acid (Zhang and
E. coli-E. coli 15-fold titer improvement
(3AB) Stephanopoulos, 2016)
22.6 mg/L titer, first de novo production (Camacho-Zaragoza et
E. coli-E. coli Resveratrol
from glycerol al. , 2016)
E. coli-E. coli Perillyl acetate (POHAc)
o f
3.3-fold titer and ~34-fold productivity
(Willrodt et al. , 2015)
ro
improvement
E. coli-E. coli Flavonoids 970-fold titer improvement (Jones et al. , 2016)
E. coli-E. coli Pinene
-p
1.9-fold titer improvement
e
(Niuet al. , 2018)
E. coli-E. coli
Salicylate
2-O-β-d-glucoside
al
89.7% of the theoretical yield,
G. oxydans-K. 2-keto-L-gulonic acid
comparable to the conventional (Wang et al. , 2016)
vulgare (2-KGA)
n
two-step fermentation
P. putida-P. putida
r
2-hydroxybiphenyl
u
(2HBP)
Up to 50% 2HBP formation (Martínez et al. , 2016)
oneidensis
J
E. coli-B. subtilis-S.
o Electricity
0.28 g of glucose was converted to
electricity (~550 mV) for more than 15
days
(Liu et al. , 2017)
E. coli-E. coli-E. coli Rosmarinic acid 38-fold titer improvement (Li et al. , 2019)
E. coli-E. coli-E. 9.5 mg/L of titer, the first report in
Callistephin (Jones et al. , 2017)
coli- E. coli non-plant host*
Eukaryote- P. pastoris- Monacolin J, 55% improvement of monacolin J and
(Liu et al. , 2018b)
Eukaryote P. pastoris Lovastatin 71%improvement of lovastatin from
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methanol
Bacteria-Eukaryote 33 mg/L vs non-detected by
E. coli-S.cerevisiae Oxygenated taxanes (Zhou et al., 2015)
monoculture
21.16 mg/L of titer, 8-fold titer
E. coli-S.cerevisiae Naringenin (Zhang et al. , 2017)
f
improvement
*No report using mono-culture de novo synthesis.
o o
p r
e -
P r
a l
r n
o u
J
Table 3. An overview of microbial consortia mediated consolidated bioprocessing (CBP) systems for bulk chemical production.
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f
E. coli &
cadaverine and Starch of cadaverine and 3.4 mM of (Sgobba et al. , 2018)
o
C. glutamicum
L-pipecolic acid L-pipecolic acid
ro
Ethanol T. reesei &
(Brethauer and Studer,
p
S. cerevisiae & wheat straw ~ 9 g/L, 67% yield
2014)
S. stipitis
C. phytofermentans & S.
e -
cerevisiae
α-cellulose
P r 22 g/L
15.2 g/L, 99% of the
(Zuroff et al. , 2013)
(Suriyachai et al. ,
S. cerevisiae & S. stipitis
Z. mobilis &
a l
Pretreated rice straw
Enzymatically hydrolysed
theoretical maximum 2013)
ur
C. tropicalis lignocellulosic biomass
Isobutanol T. reesei & E. coli Corn Stover 1.88 g/L, 62% of the
(Minty, Singer, 2013)
ABE
C. cellulovorans &
C. beijerinckii J o Corn cobs (alkali extracted)
theoretical maximum
22.1 g/L solvents (4.25 g/L
acetone, 11.5 g/L butanol and (Wen et al. , 2017)
6.37 g/L ethanol)
23.3 g/L solvents (3.7 g/L
C. beijerinckii & Biologically treated wheat (Valdez-Vazquez,
ethanol, 14.2 g/L butanol, and
C. cellulovorans straw Pérez-Rangel, 2015)
5.4 g/L acetone)
C. beijerinckii & Alkali extracted deshelled 11.8 g/L solvents (2.64 g/L
(Wen et al. , 2014)
C. cellulovorans corn cobs acetone, 8.30 g/L butanol and
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Figure legends
development.
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circuits, the LuxI-type protein catalyzes the synthesis of an N-acylhomoserine
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lactones (AHLs) autoinducer (pentagons). Once AHLs reach a threshold level in the
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environment, they will activate the transcriptional regulator proteins of LuxR family.
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The LuxR/AHL complex can activate the expression of multiple target genes,
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including those required for AHL synthesis. (b) Quorum sensing in Gram-positive
bacteria consortium. Autoinducing peptides (AIPs) are actively exported from the cell
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receptor-HK and imported into the cell, the phosphorylated AIP will bind on the target
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DNA to regulate its transcription. (c) A model of signal molecule transport using
from cell surface, which forms a spherical container. The MVs fuse with a receptor
of target genes. (d) The model of physical contact. The typical case is the intimate
of histone H3 catalyzed by the Saga/Ada complex. (e) Gene level changes in microbial
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consortia. The mixed culture can cause a serial changes in gene expression in the
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Recombinant Lignocellulolytic Strategy means expression these lignocelluloses
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degrading enzymes in solvents producing microorganisms. (c) Consolidated
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bioprocessing Strategy for lignocellulose biorefinery using microbial consortia, where
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biomass is first degraded into fermentable carbon source catalyzed by degrading
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Highlights:
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communication and gene mutation.
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Providing guidance and experience in the construction of artificial microbial
consortia systems. pr
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The outstanding challenges and future directions to advance artificial microbial
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