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Article Abstract
Biotin is an essential vitamin in plants and mammals, functioning as the carbon dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring the integrity of the carbon chain in biotin synthesis. BioW catalyzes the condensation of pimelic acid (C7 dicarboxylic acid) with CoASH in an ATP-dependent manner to form pimeloyl-CoA, the first dedicated biotin building block. Multiple structures of Bacillus subtilis BioW together capture all three substrates, as well as the intermediate pimeloyl-adenylate and product pyrophosphate (PP), indicating that the enzyme uses an internal ruler to select the correct dicarboxylic acid substrate. Both the catalytic mechanism and the surprising stability of the adenylate intermediate were rationalized through site-directed mutagenesis. Building on this understanding, BioW was engineered to synthesize high-value heptanoyl (C7) and octanoyl (C8) monocarboxylic acid-CoA and C8 dicarboxylic-CoA products, highlighting the enzyme's synthetic potential.
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BioWF: A Naturally-Fused, Di-Domain Biocatalyst from Biotin Biosynthesis Displays an Unexpectedly Broad Substrate Scope.
Chembiochem
September 2022
School of Chemistry University of Edinburgh, David Brewster Road, Edinburgh, EH9 3FJ, UK.
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Biotechnol Lett
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Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, Department of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, 237012, Anhui, People's Republic of China.
Objective: To enhance biotin production in Escherichia coli by engineering a heterologous biotin synthetic pathway.
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Nat Chem Biol
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Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Reactions that activate carboxylates through acyl-adenylate intermediates are found throughout biology and include acyl- and aryl-CoA synthetases and tRNA synthetases. Here we describe the characterization of Aquifex aeolicus BioW, which represents a new protein fold within the superfamily of adenylating enzymes. Substrate-bound structures identified the enzyme active site and elucidated the mechanistic strategy for conjugating CoA to the seven-carbon α,ω-dicarboxylate pimelate, a biotin precursor.
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Nat Chem Biol
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EastChem School of Chemistry, University of Edinburgh, Edinburgh, UK.
Article Synopsis
- Biotin is a crucial vitamin involved in lipid metabolism for both plants and mammals, acting as a carbon dioxide carrier.
- The enzyme BioW from bacteria ensures proper biotin synthesis by selectively combining pimelic acid with CoASH, forming the key building block pimeloyl-CoA.
- Researchers have manipulated BioW to create valuable synthetic products like heptanoyl-CoA and octanoyl-CoA by revealing its substrate-selection mechanisms and stability through induced mutations.
Pimelic acid, the first precursor of the Bacillus subtilis biotin synthesis pathway, exists as the free acid and is assembled by fatty acid synthesis.
Mol Microbiol
May 2017
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Biotin synthetic pathways are readily separated into two stages, synthesis of the seven carbon α, ω-dicarboxylic acid pimelate moiety and assembly of the fused heterocyclic rings. The biotin pathway genes responsible for pimelate moiety synthesis vary widely among bacteria whereas the ring synthesis genes are highly conserved. Bacillus subtilis seems to have redundant genes, bioI and bioW, for generation of the pimelate intermediate.
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