Novel Ketosynthases Catalyzing the Non-Decarboxylative Claisen Condensation

Abstract

In this review, we present the recent advances in unusual novel ketosynthases catalyzing the non-decarboxylative Claisen condensations, including CsyB, MxnB/CorB, Ppys and StlD. The differences are summarized between these non-decarboxylative ketosynthases and the typical decarboxylative ketosynthases. Furthermore, the detailed enzymatic characteristics, structural basis, and catalytic mechanismof these novel ketosynthasesare described. Finally, the prospect of these kind of ketosynthases is discussed.

A Pair of Atypical KAS III Homologues with Initiation and Elongation Functions Program the Polyketide Biosynthesis in Asukamycin

“…β‐Ketoacyl‐ACP‐forming enzymes belong to the thiolase superfamily [3b] . With a few exceptions, [4] they generally catalyze C−C bond formation in a decarboxylating condensation manner [3b, 5] . Based on the different functional roles and catalytic mechanisms, these enzymes can be primarily divided into the following classes (Figure S1): i) “initiation” enzymes, including the β‐ketoacyl‐ACP synthase III (KAS III) of fatty acid synthase (FAS) and polyketide synthases (PKS), which catalyze decarboxylative condensation between acyl‐CoA and malonyl‐ACP to yield acylacetyl‐ACP, [6] and ii) “elongation” enzymes, including the ketosynthase (KS) domain of type I FAS and PKS, [7] the KAS I/KAS II of bacterial and plant type II FAS, [8] and the KS‐CLF heterodimer of type II PKSs, [9] which catalyze the decarboxylative condensation between the ACP‐thioester and malonyl‐like ACP.…”