title: Closing in on complete pathways of biotin biosynthesis.
abstract: Biotin is an enzyme cofactor indispensable to metabolic fixation of carbon dioxide in all three domains of life. Although the catalytic and physiological roles of biotin have been well characterized, the biosynthesis of biotin remains to be fully elucidated. Studies in microbes suggest a two-stage biosynthetic pathway in which a pimelate moiety is synthesized and used to begin assembly of the biotin bicyclic ring structure. The enzymes involved in the bicyclic ring assembly have been studied extensively. In contrast the synthesis of pimelate, a seven carbon α,ω-dicarboxylate, has long been an enigma. Support for two different routes of pimelate synthesis has recently been obtained in Escherichia coli and Bacillus subtilis. The E. coli BioC-BioH pathway employs a methylation and demethylation strategy to allow elongation of a temporarily disguised malonate moiety to a pimelate moiety by the fatty acid synthetic enzymes whereas the B. subtilis BioI-BioW pathway utilizes oxidative cleavage of fatty acyl chains. Both pathways produce the pimelate thioester precursor essential for the first step in assembly of the fused rings of biotin. The enzymatic mechanisms and biochemical strategies of these pimelate synthesis models will be discussed in this review.
authors: Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S. Goodwin Ave, Urbana, Illinois 61801, USA.
authors: Steven
authors: S
authors: Lin
authors: John E
authors: JE
authors: Cronan
mesh_terms: D001412:Bacillus subtilis / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D001710:Biotin / Q000096:biosynthesis*; D003065:Coenzyme A / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010867:Pimelic Acids / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007506:Iron-Sulfur Proteins; D010867:Pimelic Acids; D001710:Biotin; D003065:Coenzyme A