title: Pimelic acid, the first precursor of the Bacillus subtilis biotin synthesis pathway, exists as the free acid and is assembled by fatty acid synthesis.
abstract: 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. Largely consistent with previous genetic studies it was found that deletion of bioW caused a biotin auxotrophic phenotype whereas deletion of bioI did not. BioW is a pimeloyl-CoA synthetase that converts pimelic acid to pimeloyl-CoA. The essentiality of BioW for biotin synthesis indicates that the free form of pimelic acid is an intermediate in biotin synthesis although this is not the case in E. coli. Since the origin of pimelic acid in Bacillus subtilis is unknown,13C-NMR studies were carried out to decipher the pathway for its generation. The data provided evidence for the role of free pimelate in biotin synthesis and the involvement of fatty acid synthesis in pimelate production. Cerulenin, an inhibitor of the key fatty acid elongation enzyme, FabF, markedly decreased biotin production by B. subtilis resting cells whereas a strain having a cerulenin-resistant FabF mutant produced more biotin. In addition, supplementation with pimelic acid fully restored biotin production in cerulenin-treated cells. These results indicate that pimelic acid originating from fatty acid synthesis pathway is a bona fide precursor of biotin in B. subtilis.
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Miglena
authors.initials: M
authors.lastname: Manandhar
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.|Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: John E
authors.identifier: 0000-0002-7064-312X
authors.initials: JE
authors.lastname: Cronan
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D001710:Biotin / Q000096:biosynthesis* / Q000378:metabolism; D003001:Cloning, Molecular; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D010867:Pimelic Acids / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000213:Acyl Carrier Protein; D000214:Acyl Coenzyme A; D005227:Fatty Acids; D010867:Pimelic Acids; C019527:pimeloyl-coenzyme A; D001710:Biotin; D003066:Coenzyme A Ligases; C077998:pimeloyl-CoA synthetase