Industrial Manufacturing of Vitamin B2

Name of School: School of Engineering and Computer Science

University: University of Hull

Student Number: 201706068

Submission Date: 26th March 2020

Abstract
-(200 words) highlight what is included in the report
Introduction

Vitamin B2 also known as Riboflavin or lactochrome or 7,8-dimethyl-10-(d-1’-ribityl)isoalloxazine is an

orange-yellow organic compound that is water-soluble it is a key ingredient in metabolic processes. Plants
and some micros organisms such as bacteria such as commensals such as Lactobacillus acidophilus and
pathogens such as Mycobacterium tuberculosis and Salmonella typhimurium are able to produce B2
through synthesis. However, like most animals’ humans need consume to B 2 as an essential nutrient.
Foods such as milk, leafy vegetables, whole grains, liver, egg white, cheese, and fresh meat. (Christine,
David 2012). Though only needed in very small amounts (for men 1.3 milligrams per day, and for
women, it is 1.1 milligram per day) B2 is essential for all animals and deficiency will cause sever medical
problems such as ariboflavinosis. Vitamin B2 cannot be stored within the body therefore a constant intake
is required. Deficiency will cause cracking of the skin at the corners of the mouth and fissuring of the lips,
swollen red beefy tongue, corneal vascularization and sensitivity of eyes to light, itching and scaling of
the facial skin. Deficiency in B2 has not been linked to a fatality. B2 plays a key part in coenzymes such as
flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). Similar to other B vitamins B 2
plays a key role in energy metabolism, metabolism of ketone bodies, carbohydrates, proteins and fats. The
important thing about flavin coenzyme is that almost all of it is reutilized. B 2 also help support the
immune and nervous system, red cell production, and the activation of vitamin B 6. B2 is considered to be
more stable then other B vitamins however it can be easily destroyed by electromagnetic radiation such as
such light and its ultraviolet rays (Christine, David 2012). Therefore, these considerations must and have
been considered for the production a B2.

Figure 1: solution of riboflavin

The History and Development of B2 Process Techniques
-History of B2 (1000 words)
The first observation of B2 is said to be of a fluorescent pigment in milk with yellow-green colour which
was first observed by the chemist Alexander Wynter Blyth in 1872, however it was not until the 1930s
that it was characterised as B2. In the second half of the 19 th century interest begun to develop in the need
for major food groups such as protein, carbohydrate, and fat to nourish our bodies and of minerals to
maintain our bone. However, the need for trace amounts of substances essential for nutrition with the
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discovery of the water-soluble vitamin, vitamin B1 also known as thaimin which would lead to
deficiencies. Early researchers in the 19th century realized that there were one or more additional water-
soluble factors, and these were called the vitamin B-2 complex. This prompted a search for similar
vitamins in food substances such as milk, yeast, whole wheat and liver. Vitamin B2 has no disease
associated with B2 deficiency however when B2 with its growth-stimulating properties of the food
extracts were given to young rats that this then enabled the vitamin to be extracted. B2 was the second
vitamin to be isolated after B1 but it was the first of the B2 complex to be isolated. Its was shown in 1939
to be an essential vitamin. Christiaan Eijkman in 1897 demonstrated that that if he fed both stale as well
as freshly cooked polished rice to chickens, he could induce a condition closely resembling the
polyneuritic symptoms of beriberi. After this Casimir Funk in 1991 is reported to be the first person to
isolate the substance in polished rice that had antiberiberi properties. As the substance he isolated had an
distiguising amino group within its structure and therefore he referred to it as ‘vital amine’. With his work
the word vitamin was introduced to descib a substance present in trace amount be essential for life.
Following this discovery, Casimir Funk (1884–1967), in 1911, was the first person to report the isolation
of a substance in rice polishings that had antiberiberi properties. As this substance could be shown to have
an amino group within its structure, he called it a ‘vital amine’. His work introduced the word ‘vitamine’
to describe a substance present in the diet in small amounts but essential for life. N o nutritional
deficiency disease like beriberi, pellagra or xerophthalmia led to the research and discovery of riboflavin.
Even today, riboflavin deficiency is probably one of the commonest nutritional deficiencies in the
developing world, yet little attention is paid to it as it is not linked to any serious clinical condition [2] .
In man, early symptoms are usually mild disturbances of the skin and mucous membranes, but
experimentally, deficiency of riboflavin in animals brings about a rapid restriction of growth. The effects
on growth may equally apply in man and delay the development of serious clinical symptoms by lowering
requirements. However, experimentally, it was the impairment of growth when animals were placed on
semi-synthetic diets that initiated the research leading to the characterization of riboflavin. I n 1879,
Alexander Wynter Blyth, an English chemist, is credited as being the first person to isolate a water-
soluble material from cow milk whey that glowed with a yellow-green fluorescence when exposed to
light and gave it the name lactochrome [3], ‘lacto’ from the milk and ‘chrome’ meaning color because of
the yellow pigment. However, at that time Blyth was not able to deter
Process routes of production of B2
-Comparison with basic knowledge of bioprocess technique, manufacturing technique, process principles
and industrial application (1000 words)
Chemical synthesis was the first production method to be established however in recent years the
production is shifting towards to producing B2 through fermentation.

Chemical Synthesis:

Fermentation:
Currently there are three main organisms used for the industrial production of B2 by fermentation; the
fliamentous Fungus Ashbya gossypii which is currently being used in BASF, Germany, the yeast Candida
fata currently be used in ADM, USA, and a genetically engineered strain of Bacillus subtilis used in
DSM, Germany.

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Figure 2: Fermentation production process of vitamin B2
At the beginning of the feed components are glucose syrup (70%), yeast, malt extract, sunflower oil,
sulfuric acid and concentrated salt solution at room temperature (25°C). Shown in figure 2 there is
preparation and sterilization of the medium. Preparation includes mixing together of components due to
the compositions sterilization of all mixed components is not possible using classical batch conditions
(121◦C, 20 minutes). Therefore, the medium would be divided into several groups: group 1. glucose and
sunflower oil, group 2. peptone, yeast and malt extracts, group 3. salts in water group 4. methionine. The
latter is sterilized by filtration. Sulfuric acid does not require sterilization. In addition to this, two
solutions are made with 1 being glucose and the other consisting of the nutrients. This is required in the
batch method used for fermentation. Before the main fermentation there is necessary seed cultures that
need to be fermented this take 50 hours while the main fermentation takes 500 hours this produces
approximately 27 g/L of B2 during this phase aeration is needed and this is delivered by a gas
compressor. After the main fermentation has be completed to the point of 10% inoculum ratio, the
process continues to the harvesting phase followed by crystallization, centrifugation (decanter) and final
drying. This produces a dry powder or granulate at 70% purity with the impurities consist of salts and
biomass.
Evaluation of the Industrial Manufacture of B2
-Life cycle assessment and sustainability of the process (1000 words)

References

Christine A. Northrop-Clewes. And David I. Thurnham (2012) Annals of Nutrition and Metabolism. The
Discovery and Characterization of Riboflavin, pp. 225-227.
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Heinzle, Elmar, Arno P. Biwer, and Charles L.Cooney (2007). Development of sustainable bioprocesses:
modeling and assessment. John Wiley & Sons.