Synthesis of the α,ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway

Abstract

Biotin synthesis requires the C7 α, ω-dicarboxylic acid, pimelic acid. Although pimelic acid was known to be primarily synthesized by a head to tail incorporation of acetate units, the synthetic mechanism was unknown. It has recently been demonstrated that in most bacteria the biotin pimelate moiety is synthesized by a modified fatty acid synthetic pathway in which the biotin synthetic intermediates are O-methyl esters disguised to resemble the canonical intermediates of the fatty acid synthetic pathway. Upon completion of the pimelate moiety, the methyl ester is cleaved. A very restricted set of bacteria have a different pathway in which the pimelate moiety is formed by cleavage of fatty acid synthetic intermediates by BioI, a member of the cytochrome P450 family.

Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters

“…In contrast to the early biosynthetic steps, the origin of pimelic acid varies across bacterial species, and has been found in various forms: as a free di-acid, a mono-methyl ester, and transformed into a pimeloyl thioester by attachment to either coenzyme A (CoASH) or an acyl carrier protein (ACP) 14 . The thioester is condensed with L-alanine in an AONScatalysed reaction to begin the late stages of biotin biosynthesis 8,13 .…”

Brucella BioR Regulator Defines a Complex Regulatory Mechanism for Bacterial Biotin Metabolism

“…In Escherichia coli, which defines the paradigm, biotin synthesis proceeds via a four-step path with pimeloyl-acyl carrier protein (ACP) as the precursor (6). Recently, we found that the generation of pimeloyl moiety in earlier steps of biotin synthesis is involved in a modified type II fatty acid biosynthetic pathway in E. coli (6)(7)(8). In the BioC-BioH pathway of pimelate synthesis, BioC methylates malonyl coenzyme A (malonyl-CoA; or ACP) and gives a methyl malonyl-thioester destined to fatty acid biosynthesis to act as a primer (6,7,9), whereas the bioH gene product demethylates the pimeloyl-ACP methyl ester to form pimeloyl-ACP after two rounds of the fatty acid elongation cycle (6,7,10).…”

Biotin biosynthesis in Mycobacterium tuberculosis: physiology, biochemistry and molecular intervention

“…Many micro-organisms, plants and fungi can synthesize biotin de novo (Cronan and Lin, 2011). In contrast, mammals are biotin auxotrophs that obtain the micronutrient from intestinal micro-flora, dietary sources and recycling (Said, 2009).…”

“…The universal biosynthetic pathway, shown in Fig. 1, converts a pimeloylthioester to biotin through the activity of four enzymes, namely 7-keto-8-aminopelargonic acid synthase (KAPAS, encoded by bioF), 7,8-diaminopelargonic acid synthase (DAPAS, encoded by bioA), dethiobiotin synthetase (DTBS, encoded by bioD), and biotin synthase (BS, encoded by bioB) (reviewed (Cronan and Lin, 2011)). Briefly, KAPAS converts a pimelate moiety to 7-keto-8-aminopelargonic acid (KAPA) using L-alanine as an amino donor.…”

“…New insights into the mechanisms employed by the model bacteria Escherichia coli have come to light, and have been reviewed recently (Cronan and Lin, 2011). Briefly, the 3-carbon chain present in malonyl CoA is extended by four additional carbon units by the fatty acid biosynthetic pathway (Fig.…”