Microbial Vitamin Production and Riboflavin Transport: Biosynthesis, Environmental Uptake, and Industrial Relevance

Introduction- Microorganisms and Vitamin Dependency:

Meals bring essential elements or other nutrients that may not be self-synthesized but nonetheless required. They nourish our cells with stored chemical energy, used as building blocks or are cofactors for complex reactions all to ensure the cells can perform at an optimal level. 

Environment deliver what an organism may need. Organisms also possess a rather extensive array of versatile transporters that can import many chemically distinct nutrients and also can perform biosynthetic reactions. Human have recognized and employed bacteria in numerous industrial settings to harness these useful reactions. In fact, most capable of pathogenic bacteria are not only able to make what they require, they also have absolute mastery of use of what host makes or environment provides.

Bacterial cells use what environment provides to synthesize different other molecules that can be used to make more cells. Host bacteria are limited by a narrow geographical range. If intestinal tract or skin is their niche, they must be crafty at utilizing what is available there.

Riboflavin-A Universal Cofactor in Life:

Some atoms like metals are stuff of stars. They can’t be made and in soluble forms they are quite scarce. So bacteria must also solve this problem. Bacteria dedicate entire gene operons for acquisition of such rare nutrients. There is a bacterial nutriverse so to say. Like human are auxotrophic for some amino acids and must acquire them from environment, some pathogenic bacteria can synthesize necessary vitamins while some cannot and have to steal from host. So bacteria have evolved transporters. 

Let us taken an example of Riboflavin vitamin which illustrates that though vitamins can be produced by microorganisms, they also uptake vitamins from environment.

All living things need riboflavin (RF), a crucial vitamin. Riboflavin is typically altered in a cell to produce flavins that are physiologically active. Flavins are common intracellular cofactors, but they have also recently drawn notice for their roles in a number of external processes.

Early research showed that the marine bacteria Marinobacter sp. secretes riboflavin and FAD as photosensitizers and may use dimethyl sulfide (DMS) as a sulfur source when exposed to light.

Later, it was postulated that Campylobacter jejuni, a human intestinal pathogen, increases the bioavailability of iron through the reduction of extracellular insoluble ferric iron (Fe3+) into soluble ferrous iron (Fe2+) and riboflavin biosynthesis enhances this assimilatory ferric reduction activity. It is well known that during extracellular electron transfer, bacterially produced riboflavin serves as an electron shuttle for iron reduction.

It is also observed in bacteria that Fe availability influences expression of Riboflavin biosynthetic genes. Also, the human gut anaerobe Faecalibacterium prausnitzi uses extracellular riboflavin and thiol groups from cisteine or glutathione in order to shuttle electrons to oxygen. 

Settlement of symbiotic relationships is also influenced by the synthesis and secretion of riboflavin by bacteria. Riboflavin and other vitamins are supplied to hosts by the gut bacterial microbiome. The large intestine is thought to be the primary site of absorption for vitamins generated by bacteria in humans.

Genetic Regulation of Riboflavin Pathways in Bacteria:

Animal cells do not possess the ability to synthesize riboflavin and are absolutely dependent on riboflavin uptake to fulfill their vitamin needs, for which they have specialized transporter proteins. However, the riboflavin biosynthesis pathway (RBP) allows plants and certain microbes to produce riboflavin from scratch. This pathway utilizes guanosin-5´triphosphate (GTP) derived from the purine biosynthesis pathway and ribulose-5-phosphate from the pentose-phosphate pathway to produce one mole of riboflavin. The production of other flavins, including FMN and FAD, then uses riboflavin as a precursor. Although the majority of bacteria can generate riboflavin, many species must absorb it from the environment utilizing specific flavin transport systems. Studies on Bacillus subtilis provided the first experimental support for riboflavin uptake in bacteria, demonstrating that a riboflavin auxotroph mutant enhanced the bacteria’s capacity to internalize radiolabeled riboflavin in comparison to the wild type strain. Since null mutants in this gene and a mutant of its paralog in Lactococcus lactis are unable to absorb riboflavin from the media, it was shown that the gene encoding RibU in B. subtilis is involved in riboflavin transport.

The widely diverse ways that bacteria genetically regulate their supply of riboflavin contrast sharply with the globally conserved demand for it. Some bacteria code for a complete RBP without any discernible gene duplication, meeting their riboflavin requirements in a straightforward way. Similarly, Streptococcus pyogenes and other riboflavin auxotrophic bacteria preserve a riboflavin transporter gene in order to absorb ambient riboflavin. Even among species that are phylogenetically related, the variety of RBP and riboflavin importer genes varies greatly, despite the fact that such occurrences demonstrate that basic riboflavin supply pathways may be adequate for certain bacteria.

Modern Biotechnological Enhancements in Vitamin Synthesis:

Microbes are utilized for industrial production of vitamins against use of plants and animal sources. Apart from avoiding high price, some of the reasons are:

  • Desired mutation can be performed in the wild strain of production organism for increasing the yield and potency of the vitamins. By employing modern techniques of genetic engineering, vitamin production can be enhanced. For instance, the protoplast fusion procedure between Rhodopseudomonas spheroides and Protaminobacter rubber can increase the production of vitamin B12 and produce a hybrid strain known as Rhodopseudomonas protamicus.
  • Microorganisms have short generation time comparatively and can be utilized for fast harvest.
  • The natural plant or animal source’s vitamin and related health component content is typically quite low and varies greatly.
  • Vitamins derived from plants and animals have an organoleptic appearance and frequently have suboptimal shelf lives.
  • When these natural food vitamin sources are extracted or otherwise altered, water-soluble vitamins are often lost.
  • (Pro)vitamins and associated health compounds are labile molecules during harvest, preservation, and storage. They are typically sensitive to heat (pyridoxine, folic acid, vitamin C, vitamin E, riboflavin, D-pantothenic acid), light (B2, B6, B9, vitamin B12, C, and vitamin D), oxygen (B9, C, and D), and pH.
  • Vitamin C, B2, B12, ergocalciferol or D2, menaquinone or K2, coenzyme Q10 or ubiquinone, pyrrolquinoline quinine or PQQ, and other vitamin-like chemicals are created (only) by microbial fermentation with bacteria, yeasts, or fungi. Certain compounds can be created by combining microbial/enzymatic and chemical processes.

References:

Crossley, R. A., Gaskin, D. J., Holmes, K., Mulholland, F., Wells, J. M., Kelly, D. J., van Vliet, A. H., & Walton, N. J. (2007). Riboflavin biosynthesis is associated with assimilatory ferric reduction and iron acquisition by Campylobacter jejuni. Applied and environmental microbiology73(24), 7819–7825. https://doi.org/10.1128/AEM.01919-07

Ross, S. M. (2017). Integrative functions of the ventral tegmental area and nucleus accumbens: Neurochemical and behavioral evidence and clinical implications. Critical Reviews in Neurobiology, 28(1), 1–83. https://doi.org/10.1080/1040841X.2016.1192578

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