BioWF: A Naturally-Fused, Di-Domain Biocatalyst from Biotin Biosynthesis Displays an Unexpectedly Broad Substrate Scope.

ABSTRACT: The carbon backbone of biotin is constructed from the C₇ di-acid pimelate, which is converted to an acyl-CoA thioester by an ATP-dependent, pimeloyl-CoA synthetase (PCAS, encoded by BioW). The acyl-thioester is condensed with ʟ-alanine in a decarboxylative, Claisen-like reaction to form an aminoketone (8-amino-7-oxononanoic acid, AON). This step is catalysed by the pyridoxal 5'-phosphate (PLP)-dependent enzyme (AON synthase, AONS, encoded by BioF). Distinct versions of Bacillus subtilis BioW (BsBioW) and E. coli BioF (EcBioF) display strict substrate specificity. In contrast, a BioW-BioF fusion from Corynebacterium amycolatum (CaBioWF) accepts a wider range of mono- and di-fatty acids. Analysis of the active site of the BsBioW : pimeloyl-adenylate complex suggested a key role fo

SUBMITTER: Richardson SM 

PROVIDER: S-EPMC9544090 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature