Biosynthesis of Biotin

Marquet, Andrée

doi:10.1016/b978-008045382-8.00136-2

Cited by 4 publications

(2 citation statements)

References 103 publications

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“…Six out of eight B-vitamins analyzed in this study, B1 (thiamin), B2 (riboflavin), B3 (niacin), B5 (pantothenate), B9 (folate) and B6 (pyridoxine), are common biosynthetic precursors of major metabolic cofactors, TPP, FMN/FAD, NAD(P), CoA, THF, and PLP, respectively, essential in all microbes as well as in the mammalian host (McCormick, 2003). Vitamin B7 (biotin) serves as an essential carboxylation/decarboxylation cofactor upon covalent attachment to biotin carboxyl carrier protein (BCCP) playing an important role in lipogenesis, carbohydrate and amino acid metabolism (Marquet, 2010). Vitamin B12 (cobalamin), a precursor of the B12 coenzyme family including cyanocobalamin, methylcobalamin, and adenosylcobalamin (AdoCbl), is essential for all animals and many, but not all bacterial species (Degnan et al, 2014; Danchin and Braham, 2017).…”

Section: Introductionmentioning

confidence: 99%

Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome

et al. 2019

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The human gut microbiome harbors a diverse array of metabolic pathways contributing to its development and homeostasis via a complex web of diet-dependent metabolic interactions within the microbial community and host. Genomics-based reconstruction and predictive modeling of these interactions would provide a framework for diagnostics and treatment of dysbiosis-related syndromes via rational selection of therapeutic prebiotics and dietary nutrients. Of particular interest are micronutrients, such as B-group vitamins, precursors of indispensable metabolic cofactors, that are produced de novo by some gut bacteria (prototrophs) but must be provided exogenously in the diet for many other bacterial species (auxotrophs) as well as for the mammalian host. Cross-feeding of B vitamins between prototrophic and auxotrophic species is expected to strongly contribute to the homeostasis of microbial communities in the distal gut given the efficient absorption of dietary vitamins in the upper gastrointestinal tract. To confidently estimate the balance of microbiome micronutrient biosynthetic capabilities and requirements using available genomic data, we have performed a subsystems-based reconstruction of biogenesis, salvage and uptake for eight B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) and queuosine (essential factor in tRNA modification) over a reference set of 2,228 bacterial genomes representing 690 cultured species of the human gastrointestinal microbiota. This allowed us to classify the studied organisms with respect to their pathway variants and infer their prototrophic vs. auxotrophic phenotypes. In addition to canonical vitamin pathways, several conserved partial pathways were identified pointing to alternative routes of syntrophic metabolism and expanding a microbial vitamin “menu” by several pathway intermediates (vitamers) such as thiazole, quinolinate, dethiobiotin, pantoate. A cross-species comparison was applied to assess the extent of conservation of vitamin phenotypes at distinct taxonomic levels (from strains to families). The obtained reference collection combined with 16S rRNA gene-based phylogenetic profiles was used to deduce phenotype profiles of the human gut microbiota across in two large cohorts. This analysis provided the first estimate of B-vitamin requirements, production and sharing capabilities in the human gut microbiome establishing predictive phenotype profiling as a new approach to classification of microbiome samples. Future expansion of our reference genomic collection of metabolic phenotypes will allow further improvement in coverage and accuracy of predictive phenotype profiling of the human microbiome.

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Section: Introductionmentioning

confidence: 99%

Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome

et al. 2019

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“…Despite its essential functions, de novo synthesis of this vitamin is restricted to bacteria, a few fungi, and plants. Thus, inhibition of the biotin synthesis pathway key enzymes is an attractive approach for antibiotic, fungicide, and herbicide development (Alban et al, 2000;Marquet, 2010). All animals, including humans, cannot synthesize biotin as part of their normal metabolism and therefore rely on the supply of biotin from exogenous sources.…”

Section: Introductionmentioning

confidence: 99%

Biochemical and Structural Characterization of the Arabidopsis Bifunctional Enzyme Dethiobiotin Synthetase–Diaminopelargonic Acid Aminotransferase: Evidence for Substrate Channeling in Biotin Synthesis

et al. 2012

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Diaminopelargonic acid aminotransferase (DAPA-AT) and dethiobiotin synthetase (DTBS) catalyze the antepenultimate and the penultimate steps, respectively, of biotin synthesis. Whereas DAPA-AT and DTBS are encoded by distinct genes in bacteria, in biotin-synthesizing eukaryotes (plants and most fungi), both activities are carried out by a single enzyme encoded by a bifunctional gene originating from the fusion of prokaryotic monofunctional ancestor genes. In few angiosperms, including Arabidopsis thaliana, this chimeric gene (named BIO3-BIO1) also produces a bicistronic transcript potentially encoding separate monofunctional proteins that can be produced following an alternative splicing mechanism. The functional significance of the occurrence of a bifunctional enzyme in biotin synthesis pathway in eukaryotes and the relative implication of each of the potential enzyme forms (bifunctional versus monofunctional) in the plant biotin pathway are unknown. In this study, we demonstrate that the BIO3-BIO1 fusion protein is the sole protein form produced by the BIO3-BIO1 locus in Arabidopsis. The enzyme catalyzes both DAPA-AT and DTBS reactions in vitro and is targeted to mitochondria in vivo. Our biochemical and kinetic characterizations of the pure recombinant enzyme show that in the course of the reaction, the DAPA intermediate is directly transferred from the DAPA-AT active site to the DTBS active site. Analysis of several structures of the enzyme crystallized in complex with and without its ligands reveals key structural elements involved for acquisition of bifunctionality and brings, together with mutagenesis experiments, additional evidences for substrate channeling.

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Andrée Marquet (1934–)

Fauque

Marquet²

2011

European Women in Chemistry

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Biosynthesis of Biotin

Cited by 4 publications

References 103 publications

Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome

Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome

Biochemical and Structural Characterization of the Arabidopsis Bifunctional Enzyme Dethiobiotin Synthetase–Diaminopelargonic Acid Aminotransferase: Evidence for Substrate Channeling in Biotin Synthesis

Andrée Marquet (1934–)

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