To elucidate the general biosynthetic pathway of fungal dimeric anhydrides, a gene cluster for the biosynthesis of the antihy-percholesterolemic agent phomoidride was identified by heterologous expression of candidate genes encoding the highly reducing polyketide synthase, alkylcitrate synthase (ACS), and alkylcitrate dehydratase (ACDH). An in vitro analysis of ACS and ACDH revealed that they give rise to anhydride monomers. Based on the established monomer biosynthesis, we propose a general biogenesis of dimeric anhydrides involving a single donor unit and four acceptor units.
To elucidate the
biosynthesis of a fungicidal dimeric anhydride zopfiellin, the putative
biosynthetic gene cluster was identified. We conducted heterologous
expression of candidate genes for the synthesis of maleic anhydride
and its dimerization and identified the two isomeric dimers with 9-membered
rings as products. Notably, α-ketoglutarate-dependent dioxygenase
ZopK oxidized one of the dimers, giving the 8-membered ring of zopfiellin.
The mechanism of oxidative rearrangement is proposed by analyzing
the incorporation of 13C-labeled precursors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.