Abstract
Pimelic acid, a seven carbon α,ω-dicarboxylic acid (heptanedioic acid), is known to provide seven of the ten biotin carbon atoms including all those of the valeryl side chain. Distinct pimelate synthesis pathways were recently elucidated in Escherichia coli and Bacillus subtilis where fatty acid synthesis plus dedicated biotin enzymes produce the pimelate moiety. In contrast, the α-proteobacteria which include important plant and mammalian pathogens plus plant symbionts, lack all of the known pimelate synthesis genes and instead encode bioZ genes. Here we report a pathway in which BioZ proteins catalyze a 3-ketoacyl-acyl carrier protein (ACP) synthase III-like reaction to produce pimeloyl-ACP with five of the seven pimelate carbon atoms being derived from glutaryl-CoA, an intermediate in lysine degradation. Agrobacterium tumefaciens strains either deleted for bioZ or which encode a BioZ active site mutant are biotin auxotrophs, as are strains defective in CaiB which catalyzes glutaryl-CoA synthesis from glutarate and succinyl-CoA.
Highlights
Pimelic acid, a seven carbon α,ω-dicarboxylic acid, is known to provide seven of the ten biotin carbon atoms including all those of the valeryl side chain
In α-proteobacteria and a few other bacteria, fabH homologs are found within biotin synthesis gene clusters, whereas the canonical fabH genes are clustered with fatty acid and phospholipid synthesis genes
The amino-acid sequences of BioZ proteins indicate conservation of the canonical FabH Cys-His-Asn catalytic triad (Fig. 2b). These investigators[16] confirmed the role of BioZ in biotin synthesis by inactivation of bioZ in Mesorhizobium loti sp. strain R7A ( Mesorhizobium japonicum22), which resulted in biotin auxotrophy
Summary
A seven carbon α,ω-dicarboxylic acid (heptanedioic acid), is known to provide seven of the ten biotin carbon atoms including all those of the valeryl side chain. Diverse pathways exist for the synthesis of the pimelate moiety precursor The known pathways, those of Escherichia coli and Bacillus subtilis, involve enzymes of fatty-acid synthesis[5,6] (Fig. 1). Instead the pimeloyl-CoA ligase (BioW) plays a key role in biotin synthesis[12] (Fig. 1b) Another proposed approach to obtain the pimelate moiety is to condense three molecules of malonate in two decarboxylative Claisen-like condensations to obtain pimeloyl-ACP13. The hydrophobicity of the active sites evident in crystal structures of fatty-acid synthetic enzymes argued that the postulated free carboxyl group would not be tolerated This dilemma is avoided in many bacteria by the pathway first demonstrated in E. coli[5,14,15] in which the free carboxyl group of malonyl-ACP is methylated by BioC, a SAM-dependent methyltransferase
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