In vitro studies of maleidride-forming enzymes

Abstract

In vitro synthesis of byssochkamic acid 12 was achieved from hexenoyl CoA 14dvia anhydride 1.

Maleidride biosynthesis – construction of dimeric anhydrides – more than just heads or tails

“…75,90,96,101 Moving beyond the monomer, the core enzyme required for dimerisation, and therefore ultimately controlling the structure of the mature maleidride, is the maleidride dimerising cyclase. 50,75,96,101,105 This coupling reaction appears to be aided by the PEBP-like enzymes, although their exact role is currently obscure. 50,75,96,101,105 The precise detail of how cyclisation is controlled remains cryptic, at present it is not possible to predict whether a biosynthetic gene cluster will deliver dimers showing head-to-head, head-to-tail or head-toside modes of cyclisation, highlighting that there is still much to be discovered in this type of pathway.…”

“…12) is essential, as no Interestingly, all conrmed and putative maleidride BGCs contain a hydrolase homologue, suggesting that it is important for the biosynthesis of maleidride compounds. 96 In vitro studies by Cox and co-workers 101 showed that the P. fulvus hydrolase, BfL1, catalysed the hydrolysis of a series of a thiol esters, rather than being ACP-selective, therefore exactly how selectivity is controlled is unknown. 101 Investigations into the ACS and ACDH enzymes through in vitro characterisation have also been reported.…”

“…96 In vitro studies by Cox and co-workers 101 showed that the P. fulvus hydrolase, BfL1, catalysed the hydrolysis of a series of a thiol esters, rather than being ACP-selective, therefore exactly how selectivity is controlled is unknown. 101 Investigations into the ACS and ACDH enzymes through in vitro characterisation have also been reported. 101 Comparison of 104a to synthetic standards revealed that the enzyme product is exclusively the anti diastereomer.…”

“…101 Investigations into the ACS and ACDH enzymes through in vitro characterisation have also been reported. 101 Comparison of 104a to synthetic standards revealed that the enzyme product is exclusively the anti diastereomer. 101 The synthesis of citrate is catalysed in most organisms by a Si-citrate synthase, with known Re-citrate synthases phylogenetically unrelated to Si-citrate synthases.…”

“…101 Comparison of 104a to synthetic standards revealed that the enzyme product is exclusively the anti diastereomer. 101 The synthesis of citrate is catalysed in most organisms by a Si-citrate synthase, with known Re-citrate synthases phylogenetically unrelated to Si-citrate synthases. 102 A structural model of BfL2 was built based on the primary metabolism citrate synthase from Acetobacter aceti, 103 which is phylogenetically related to other Si-citrate synthases.…”