[Biosynthesis of fat-soluble vitamins].

Vitamins are the essential organic substances to ensure the normal life activities of the human body. At present, vitamins are widely used in the pharmaceutical, food, animal farming, beauty and other industries, appearing in increasing application scenarios. Accordingly, the global demand for vitamins has also increased greatly. The current methods of vitamin production mainly include chemical synthesis and biosynthesis, with the latter being greener, more environmentally friendly, safer, and lower in energy consumption. Establishing the method for the biosynthesis of vitamins is of great scientific significance for achieving the goals of low carbon, energy saving, and emission reduction, as well as carbon emission peak and carbon neutrality in China. This paper reviews the research progress in the biosynthesis of vitamins, especially fat-soluble vitamins (vitamins A, D, E, and K), in recent years.

[Advances in the microbial synthesis of active ingredients in cosmetics].

With the rapid development of the medical beauty industry, functional skin care products become increasingly popular. The functions of cosmetics mainly depend on the active ingredients, which are mainly proteins, peptides, polysaccharides, phenolic acids, terpenes, vitamins, and amino acids. These active ingredients endow cosmetics with skin repairing, moistening, whitening, UV protecting, and anti-aging effects. They are mainly obtained through biological extraction and chemical synthesis. In recent years, with the development of biomanufacturing, microbial synthesis of active ingredients in cosmetics has been widely studied and applied. This article reviews the research progresses in the production of natural products including collagens, peptides, hyaluronic acid, polyphenols, terpenes, and vitamins by microbial synthetic biotechnology. Moreover, this article highlighted the synthetic pathways, metabolic regulation, and prospects of the natural products, providing a reference for subsequent microbial synthesis of active ingredients in cosmetics.

[Biosynthesis of water-soluble vitamins].

Vitamins are a class of organic substances essential for maintaining the normal physiological function of organisms. Most vitamins cannot be synthesized by the human body, and a small number of vitamins can only be synthesized in a limited manner, which cannot meet the body needs. Therefore, people need to take food or drugs containing vitamins to meet the body needs. Nowadays, vitamins are widely used in medicine, food or feed additives, cosmetics and other industries, and the demand for vitamins is growing. Vitamins are mainly produced by chemical synthesis and biosynthesis. Compared with chemical synthesis, biosynthesis of vitamins is praised for the environmental friendliness, high safety, and low costs. Therefore, it is of great practical significance to study the biosynthesis methods of vitamins. This paper reviews the research progress in the methods and summarizes the research results in the biosynthesis of water-soluble vitamins (B vitamins and vitamin C) in recent years and then makes an outlook on the future development in this field.

[Enzyme metabolism and functions in vitamin biosynthesis pathways].

Vitamins, as indispensable organic compounds in life activities, demonstrate a complex and refined metabolic network in organisms. This network involves the coordination of multiple enzymes and the integration of various metabolic pathways. Despite the achievements in metabolic engineering and catalytic mechanism research, the lack of studies regarding detailed enzymatic properties for a large number of key enzymes limits the enhancement of vitamin production efficiency and hinders the in-depth understanding and optimization of vitamin synthesis mechanisms. Such limitations not only restrict the industrial application of vitamins but also impede the development of related bio-technologies. This study comprehensively reviews the research progress in the enzymes involved in vitamin biosynthesis and details the current status of research on the enzymes of 13 vitamin synthesis pathways, including their catalytic mechanisms, kinetic properties, and applications in biology. In addition, this study compares the properties of enzymes involved in vitamin metabolic pathways and the glycolysis pathway, and reveals the characteristics of catalytic efficiency and substrate affinity of enzymes in vitamin synthesis pathways. Furthermore, this study discusses the potential and prospects of applying deep learning methods to the research on properties of enzymes associated with vitamin biosynthesis, giving new insights into the production and optimization of vitamins.

Air pollutants are negatively associated with vitamin D-synthesizing UVB radiation intensity on the ground.

Atmospheric levels of pollutants may reduce the UVB intensity at the earth's surface, with a subsequent reduction in cutaneous vitamin D synthesis. We investigated the association of various pollutants with UVB intensity on the ground. Four-year data obtained from four weather stations from across Kuwait were analyzed by median regression. Pollutants that were negatively associated with UVB were [ß (95% CI)]: benzene [- 2.61 (- 4.13, - 1.09)], ethyl-benzene [- 2.20 (- 3.15, - 1.25)], ozone [- 0.23 (- 0.28, - 0.17)], nitric oxide [- 0.11 (- 0.15, - 0.06)], sulfur dioxide [- 0.10 (- 0.17, - 0.04)] and particulate matter PM10 [- 0.002 (- 0.003, - 0.002)]. Pollutants that were negatively associated with the UVB/UVA ratio were [ß (95% CI)]: benzene [- 15.57 (- 24.94, - 6.20)], nitric oxide [- 0.53 (- 0.81, - 0.25)], ozone [- 0.38 (- 0.70, - 0.06)], and total hydrocarbon [- 0.02 (- 0.04, - 0.01)]. Furthermore, benzene and nitric oxide levels were higher in the morning and evening hours, which are the times of most solar exposure in this region due to high temperature during midday. In addition to other known factors, attenuation of UVB by these pollutants may contribute to lower vitamin D levels in populations. In addition to direct public health hazard, these pollutants may contribute to the very high prevalence of VDD in this region.

Microbial factories: monitoring vitamin B2 production by Escherichia coli in microfluidic cultivation chambers.

Microbial cells represent a standard production host for various important biotechnological products. Production yields can be increased by optimising strains and growth conditions and understanding deviations in production rates over time or within the microbial population. We introduce here microfluidic cultivation chambers for highly parallel studies on microbial cultures, enabling continuous biosynthesis monitoring of the industrially relevant product by Escherichia coli cells. The growth chambers are defined by ring-valves that encapsulate a volume of 200 pL when activated. Bacterial cells, labelled with magnetic beads, are inoculated in a small magnetic trap, positioned in the centre of each chamber. Afterwards, the ring-valves are partially activated, allowing for exchange reagents, such as the addition of fresh media or specific inducers of biosynthesis, while the bacterial cells and their progeny are maintained inside. On this platform, we monitor the production of riboflavin (vitamin B2). We used different variants of a riboflavin-overproducing bacterial strain with different riboflavin production levels and could distinguish them on the level of individual micro-colonies. In addition, we could also observe differences in the bacterial morphology with respect to the production. The presented platform represents a flexible microfluidic tool for further studies of microbial cell factories.

Potential roles of 1,5-anhydro-D-fructose in modulating gut microbiome in mice.

The gut microbiota has tremendous potential to affect the host's health, in part by synthesizing vitamins and generating nutrients from food that is otherwise indigestible by the host. 1,5-Anhydro-D-fructose (1,5-AF) is a monosaccharide with a wide range of bioactive potentials, including anti-oxidant, anti-inflammatory, and anti-microbial effects. Based on its potential benefits and minimal toxicity, it is anticipated that 1,5-AF will be used as a dietary supplement to support general health. However, the effects of 1,5-AF on the gut microbiota are yet to be clarified. Here, using an unbiased metagenomic approach, we profiled the bacterial taxa and functional genes in the caecal microbiota of mice fed a diet containing either 2% 1,5-AF or a reference sweetener. Supplementation with 1,5-AF altered the composition of the gut microbiota, enriching the proportion of Faecalibacterium prausnitzii. 1,5-AF also altered the metabolomic profile of the gut microbiota, enriching genes associated with nicotinamide adenine dinucleotide biosynthesis. These findings support the potential benefits of 1,5-AF, but further studies are required to clarify the impact of 1,5-AF on health and disease.

Recent update on lactic acid bacteria producing riboflavin and folates: application for food fortification and treatment of intestinal inflammation.

Lactic acid bacteria (LAB), widely used as starter cultures for the fermentation of a large variety of food, can improve the safety, shelf life, nutritional value and overall quality of the fermented products. In this regard, the selection of strains delivering health-promoting compounds is now the main objective of many researchers. Although most LAB are auxotrophic for several vitamins, it is known that certain strains have the capability to synthesize B-group vitamins. This is an important property since humans cannot synthesize most vitamins, and these could be obtained by consuming LAB fermented foods. This review discusses the use of LAB as an alternative to fortification by the chemical synthesis to increase riboflavin and folate concentrations in food. Moreover, it provides an overview of the recent applications of vitamin-producing LAB with anti-inflammatory/antioxidant activities against gastrointestinal tract inflammation. This review shows the potential uses of riboflavin and folates producing LAB for the biofortification of food, as therapeutics against intestinal pathologies and to complement anti-inflammatory/anti-neoplastic treatments.

Regulation of Plant Vitamin Metabolism: Backbone of Biofortification for the Alleviation of Hidden Hunger.

Micronutrient deficiencies include shortages of vitamins and minerals. They affect billions of people and are associated with long-range effects on health, learning ability, and huge economic losses. Biofortification of multiple micronutrients can play an important role in combating malnutrition. The challenge, however, is to balance plant growth with nutrient requirements for humans. Here, we summarize the major progress about vitamin biosynthesis and its response to the changing environment. We discuss the interactions among vitamins as well as possible strategies for vitamin biofortification. Finally, we propose to integrate new breeding technologies with metabolic pathway modification to facilitate the biofortification of crops, thereby alleviating the hidden hunger of target populations.

Sunlight, Vitamin D, and Xeroderma Pigmentosum.

Sunlight, in particular UV-B radiation, is an important factor for endogenous vitamin D production as 80-90% of the required vitamin D needs to be photosynthesized in the skin. The active form of vitamin D, vitamin D3 or calcitriol, binds to the ligand-activated transcription factor vitamin D receptor (VDR) for genomic and non-genomic effects. Recently, calcitriol and analogs have been shown to have antiproliferative effects in mouse and human BCC and SCC cell lines in vitro. As UV radiation plays a critical role in the photosynthesis of vitamin D, stringent sun protection, as recommended for xeroderma pigmentosum (XP) patients, may impact their vitamin D levels.XP is a rare autosomal recessive disorder with a worldwide prevalence of 1 in 1,000,000. XP can be divided into seven different complementation groups: XP-A to XP-G. The complementation groups correspond with the underlying gene defect. Defects in these genes lead to a defective nucleotide excision repair (NER), which is necessary to remove UV-induced DNA damage such as the UV photoproducts cyclobutane pyrimidine dimers (CPD) and 6-4 pyrimidine-pyrimidone (6-4 PP) dimer. Additionally, a variant form with a mutation in the translational polymerase η gene (PolH), also called XP variant (XPV), exists. Patients with XPV show a defect in translesion synthesis. Due to their inability to repair UV-induced lesions, XP patients exhibit an increased risk for UV-induced nonmelanoma skin cancer (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as well as melanoma. Although no curative therapy for XP exists today, numerous options for the treatment and prophylaxis of skin cancer have become available.

Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine.

Due to its clear inherited backgrounds as well as simple and diverse genetic manipulation systems, Bacillus subtilis is the key Gram-positive model bacterium for studies on physiology and metabolism. Furthermore, due to its highly efficient protein secretion system and adaptable metabolism, it has been widely used as a cell factory for microbial production of chemicals, enzymes, and antimicrobial materials for industry, agriculture, and medicine. In this mini-review, we first summarize the basic genetic manipulation tools and expression systems for this bacterium, including traditional methods and novel engineering systems. Secondly, we briefly introduce its applications in the production of chemicals and enzymes, and summarize its advantages, mainly focusing on some noteworthy products and recent progress in the engineering of B. subtilis. Finally, this review also covers applications such as microbial additives and antimicrobials, as well as biofilm systems and spore formation. We hope to provide an overview for novice researchers in this area, offering them a better understanding of B. subtilis and its applications.

Vitamin Biosynthesis by Human Gut Butyrate-Producing Bacteria and Cross-Feeding in Synthetic Microbial Communities.

We investigated the requirement of 15 human butyrate-producing gut bacterial strains for eight B vitamins and the proteinogenic amino acids by a combination of genome sequence analysis and in vitro growth experiments. The Ruminococcaceae species Faecalibacterium prausnitzii and Subdoligranulum variabile were auxotrophic for most of the vitamins and the amino acid tryptophan. Within the Lachnospiraceae, most species were prototrophic for all amino acids and several vitamins, but biotin auxotrophy was widespread. In addition, most of the strains belonging to Eubacterium rectale and Roseburia spp., but few of the other Lachnospiraceae strains, were auxotrophic for thiamine and folate. Synthetic coculture experiments of five thiamine or folate auxotrophic strains with different prototrophic bacteria in the absence and presence of different vitamin concentrations were carried out. This demonstrated that cross-feeding between bacteria does take place and revealed differences in cross-feeding efficiency between prototrophic strains. Vitamin-independent growth stimulation in coculture compared to monococulture was also observed, in particular for F. prausnitzii A2-165, suggesting that it benefits from the provision of other growth factors from community members. The presence of multiple vitamin auxotrophies in the most abundant butyrate-producing Firmicutes species found in the healthy human colon indicates that these bacteria depend upon vitamins supplied from the diet or via cross-feeding from other members of the microbial community.IMPORTANCE Microbes in the intestinal tract have a strong influence on human health. Their fermentation of dietary nondigestible carbohydrates leads to the formation of health-promoting short-chain fatty acids, including butyrate, which is the main fuel for the colonic wall and has anticarcinogenic and anti-inflammatory properties. A good understanding of the growth requirements of butyrate-producing bacteria is important for the development of efficient strategies to promote these microbes in the gut, especially in cases where their abundance is altered. The demonstration of the inability of several dominant butyrate producers to grow in the absence of certain vitamins confirms the results of previous in silico analyses. Furthermore, establishing that strains prototrophic for thiamine or folate (butyrate producers and non-butyrate producers) were able to stimulate growth and affect the composition of auxotrophic synthetic communities suggests that the provision of prototrophic bacteria that are efficient cross feeders may stimulate butyrate-producing bacteria under certain in vivo conditions.

Biosynthesis and accumulation of multi-vitamins in black sweet corn (Zea mays L.) during kernel development.

BACKGROUND: Black sweet corn as an edible fruit has various nutritional qualities. This study discusses changes in the vitamin C and E, folate, and carotenoid content during black sweet corn maturation, and also the effects of preharvest weather conditions and of related genes in multi-vitamin biosynthesis pathways. RESULTS: Most vitamin levels improved, especially vitamin C and carotenoid levels, while the folate content dropped rapidly. Transcript levels of most genes in folate biosynthesis showed trends that were similar to the content changes. VTC2 and GLDH, which are regulated by light, had high expression levels leading to an increase in ascorbate content during maturation. γ-Tocotrienol is the main vitamin E component, and HGGT, the key gene controlling the synthesis of tocotrienols, had a much higher expression level than other genes. Lutein and zeaxanthin were the dominant carotenoid components. A rapid reduction in the transcription level of LCYε could result in a lower lutein production rate . CONCLUSION: Black sweet corn has a high nutritional value and is rich in vitamins, including zeaxanthin, γ-tocotrienols, and ascorbic acid. The best harvest time is between 20-25 days after pollination (DAPs) when kernels had a good taste as well as relatively high vitamin levels. © 2020 Society of Chemical Industry.

Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment.

Lactic acid bacteria (LAB) can be used to increase the folate in foods by in situ fortification. Seventy LAB were screened for their ability to produce folate during growth in de Man, Rogosa and Sharpe/M17 broth. Lactobacillus casei, Lactobacillus plantarum, Lactobacillus paracasei subsp. paracasei, Lactobacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus, Lactococcus lactis subsp. lactis, Enterococcus faecium and Enterococcus lactis were able to synthetize folates in the medium, even if to a different extent. The 47 folate-producing strains were further analyzed by microbiological assay, for total, extra and intracellular folate. Enterococcus faecium VC223 and E. lactis BT161 were able to produce in cultural medium 123,625.74 ± 8.00 ng/ml and 384.22 ± 5.00 ng/ml of folate, respectively. Five strains were further examined for their ability to synthesize folate in cheese. The folate content increased with ripening up to by 54% after 30 d when L. casei VC199 was used and up to 108% and 113% after 60 d, with L. paracasei SE160 and E. lactis BT161 respectively exceeding 100 ng/100g. Results encourage the use of specific LAB to obtain natural folate bio-enriched dairy products improving folate intake.

Application of vitamin-producing lactic acid bacteria to treat intestinal inflammatory diseases.

Recent studies have shown that inflammatory diseases are becoming more frequent throughout the world. The causes of these disorders are multifactorial and include genetic, immunological, and environmental factors, and intestinal microbiota dysbiosis. The use of beneficial microorganisms has shown to be useful in the prevention and treatment of disorders such as colitis, mucositis, and even colon cancer by their immune-stimulating properties. It has also been shown that certain vitamins, especially riboflavin and folate derivatives, have proven to be helpful in the treatment of these diseases. The application of vitamin-producing lactic acid bacteria, especially strains that produce folate and riboflavin together with immune-stimulating strains, could be used as adjunct treatments in patients suffering from a wide range of inflammatory diseases since they could improve treatment efficiency and prevent undesirable side effects in addition to their nutrition values. In this review, the most up to date information on the current knowledge and uses of vitamin-producing lactic acid bacteria is discussed in order to stimulate further studies in this field.

Vitamin-guanosine monophosphate conjugates for in vitro transcription priming.

Expanding the catalytic repertoire of ribozymes to include vitamin synthesis requires efficient labelling of RNA with the substrate of interest, prior to in vitro selection. For this purpose, we rationally designed and synthesized six GMP-conjugates carrying a synthetic pre-thiamine or biotin precursor and investigated their transcription incorporation properties by T7 RNA polymerase.

Vitamin requirements and biosynthesis in Saccharomyces cerevisiae.

Chemically defined media for yeast cultivation (CDMY) were developed to support fast growth, experimental reproducibility, and quantitative analysis of growth rates and biomass yields. In addition to mineral salts and a carbon substrate, popular CDMYs contain seven to nine B-group vitamins, which are either enzyme cofactors or precursors for their synthesis. Despite the widespread use of CDMY in fundamental and applied yeast research, the relation of their design and composition to the actual vitamin requirements of yeasts has not been subjected to critical review since their first development in the 1940s. Vitamins are formally defined as essential organic molecules that cannot be synthesized by an organism. In yeast physiology, use of the term "vitamin" is primarily based on essentiality for humans, but the genome of the Saccharomyces cerevisiae reference strain S288C harbours most of the structural genes required for synthesis of the vitamins included in popular CDMY. Here, we review the biochemistry and genetics of the biosynthesis of these compounds by S. cerevisiae and, based on a comparative genomics analysis, assess the diversity within the Saccharomyces genus with respect to vitamin prototrophy.

Characterization of key bacterial species in the Daphnia magna microbiota using shotgun metagenomics.

The keystone zooplankton Daphnia magna has recently been used as a model system for understanding host-microbiota interactions. However, the bacterial species present and functions associated with their genomes are not well understood. In order to understand potential functions of these species, we combined 16S rRNA sequencing and shotgun metagenomics to characterize the whole-organism microbiota of Daphnia magna. We assembled five potentially novel metagenome-assembled genomes (MAGs) of core bacteria in Daphnia magna. Genes involved in host colonization and immune system evasion were detected across the MAGs. Some metabolic pathways were specific to some MAGs, including sulfur oxidation, nitrate reduction, and flagellar assembly. Amino acid exporters were identified in MAGs identified as important for host fitness, and pathways for key vitamin biosynthesis and export were identified across MAGs. In total, our examination of functions in these MAGs shows a diversity of nutrient acquisition and metabolism pathways present that may benefit the host, as well as genomic signatures of host association and immune system evasion.

Serial horizontal transfer of vitamin-biosynthetic genes enables the establishment of new nutritional symbionts in aphids' di-symbiotic systems.

Many insects depend on obligate mutualistic bacteria to provide essential nutrients lacking from their diet. Most aphids, whose diet consists of phloem, rely on the bacterial endosymbiont Buchnera aphidicola to supply essential amino acids and B vitamins. However, in some aphid species, provision of these nutrients is partitioned between Buchnera and a younger bacterial partner, whose identity varies across aphid lineages. Little is known about the origin and the evolutionary stability of these di-symbiotic systems. It is also unclear whether the novel symbionts merely compensate for losses in Buchnera or carry new nutritional functions. Using whole-genome endosymbiont sequences of nine Cinara aphids that harbour an Erwinia-related symbiont to complement Buchnera, we show that the Erwinia association arose from a single event of symbiont lifestyle shift, from a free-living to an obligate intracellular one. This event resulted in drastic genome reduction, long-term genome stasis, and co-divergence with aphids. Fluorescence in situ hybridisation reveals that Erwinia inhabits its own bacteriocytes near Buchnera's. Altogether these results depict a scenario for the establishment of Erwinia as an obligate symbiont that mirrors Buchnera's. Additionally, we found that the Erwinia vitamin-biosynthetic genes not only compensate for Buchnera's deficiencies, but also provide a new nutritional function; whose genes have been horizontally acquired from a Sodalis-related bacterium. A subset of these genes have been subsequently transferred to a new Hamiltonella co-obligate symbiont in one specific Cinara lineage. These results show that the establishment and dynamics of multi-partner endosymbioses can be mediated by lateral gene transfers between co-ocurring symbionts.

Comparative Genomics Guides Elucidation of Vitamin B12 Biosynthesis in Novel Human-Associated Akkermansia Strains.

Akkermansia muciniphila is a mucin-degrading bacterium found in the gut of most humans and is considered a "next-generation probiotic." However, knowledge of the genomic and physiological diversity of human-associated Akkermansia sp. strains is limited. Here, we reconstructed 35 metagenome-assembled genomes and combined them with 40 publicly available genomes for comparative genomic analysis. We identified at least four species-level phylogroups (AmI to AmIV), with distinct functional potentials. Most notably, we identified genes for cobalamin (vitamin B12) biosynthesis within the AmII and AmIII phylogroups. To verify these predictions, 10 Akkermansia strains were isolated from adults and screened for vitamin B12 biosynthesis genes via PCR. Two AmII strains were positive for the presence of cobalamin biosynthesis genes, while all 9 AmI strains tested were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups, since cobalamin is an essential cofactor in propionate metabolism. Results showed that the AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of vitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium. Lastly, two bioassays were used to confirm vitamin B12 production by the AmII phylogroup. This novel physiological trait of human-associated Akkermansia strains may affect how these bacteria interact with the human host and other members of the human gut microbiome.IMPORTANCE There is significant interest in the therapeutic and probiotic potential of the common gut bacterium Akkermansia muciniphila However, knowledge of both the genomic and physiological diversity of this bacterial lineage is limited. Using a combination of genomic, molecular biological, and traditional microbiological approaches, we identified at least four species-level phylogroups with differing functional potentials that affect how these bacteria interact with both their human host and other members of the human gut microbiome. Specifically, we identified and isolated Akkermansia strains that were able to synthesize vitamin B12 The ability to synthesize this important cofactor broadens the physiological capabilities of human-associated Akkermansia strains, fundamentally altering our understanding of how this important bacterial lineage may affect human health.