Biotin is an essential vitamin in plants and mammals functioning as the carbon dioxide carrier
within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (PCAS) acts as a highly
specific substrate selection gate ensuring the integrity of the carbon chain in biotin synthesis.
PCAS catalyses 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.
Multiple structures of Bacillus subtilis PCAS together capture all three substrates as well as
the intermediate pimeloyl-adenylate and product pyrophosphate (PPi). The enzyme uses an
internal ruler to select the correct dicarboxylic acid substrate. Site directed mutagenesis has
rationalised both the catalytic mechanism and the surprising stability of the adenylate
intermediate. Building on this understanding, PCAS has been engineered to synthesise high
value heptanoyl (C7) and octanoyl (C8) mono carboxylic acid-CoA and C8 dicarboxylic- CoA products highlighting the synthetic potential of PCAS. Data relating to the publication Wang et al.
Wang, Menglu; Campopiano, Dominic; Pipier, Andrew; Kelly, Van; Harrison, Peter. (2016). Using the pimeloyl-CoA synthetase adenylation fold to synthesise fatty acid thioesters, [dataset]. University of Edinburgh, School of Chemistry. http://dx.doi.org/10.7488/ds/1560.