EC Number   |
General Information |
Reference |
|---|
    6.2.1.14 | evolution |
Aquifex aeolicus BioW represents a distinct protein fold within the superfamily of adenylating enzymes |
745845 |
| 6.2.1.14 | evolution |
the biotin pathway genes responsible for pimelate moiety synthesis vary widely among bacteria whereas the ring synthesis genes are highly conserved. 6-Carboxyhexanoate-CoA ligase is essential in Bacillus subtilis, encoded by gene bioW, while it is not in Escherchia coli |
-, 745791 |
| 6.2.1.14 | malfunction |
BioW activity to hydrolyze adenylates of noncognate substrates can be abolished by mutation of a single residue, R159A |
745845 |
| 6.2.1.14 | malfunction |
deletion of bioW causes a biotin auxotrophic phenotype whereas deletion of bioI does not. Growth phenotypes of Bacillus subtilis bioW and bioI mutant strains, biotin auxotrophy due to bioW inactivation, overview |
-, 745791 |
| 6.2.1.14 | metabolism |
the enzyme catalyzes the first committed step of biotin biosynthesis, overview. 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. Pimelic acid originating from fatty acid synthesis pathway is a bona fide precursor of biotin in Bacillus subtilis. Synthesis of pimelate depends on fatty acid synthesis in Bacillus subtilis |
-, 745791 |
| 6.2.1.14 | more |
residues controlling substrate binding and catalysis include Tyr199, Tyr211, Arg213 and Arg227 |
-, 745844 |
| 6.2.1.14 | more |
structure-function relationship |
-, 745845 |
| 6.2.1.14 | more |
substrate-bound structures are determined to identify the enzyme active site and elucidate the mechanistic strategy for conjugating CoA to the seven-carbon alpha,omega-dicarboxylate pimelate, a biotin precursor. Proper position of reactive groups for the two half-reactions is achieved solely through movements of active site residues as confirmed by site-directed mutational analysis. The ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent of pre-transfer proofreading observed in some tRNA synthetases. BioW can carry out three different biologically prevalent chemical reactions (adenylation, thioesterification, and proofreading) in the context of another protein fold. The movement of Arg159, which serves to position this residue to assist in thioester formation, is reminiscent of the domain movement in acetyl-CoA synthetase that positions a catalytic lysine important for adenylation away from the active site to facilitate thioester formation |
745845 |
| 6.2.1.14 | physiological function |
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 |
-, 745844 |
| 6.2.1.14 | physiological function |
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. Bacillus subtilis has redundant genes, bioI and bioW, for generation of the pimelate intermediate. Expression of either Bacillus subtilis BioW or BioI bypasses the biotin auxotrophy of an Escherichia coli DELTAbioC DELTAbioH mutant strain SLT25 |
-, 745791 |
