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An Unusual Type II Polyketide Synthase System Involved in Cinnamoyl Lipid Biosynthesis
Author(s) -
Deng Zirong,
Liu Jing,
Li Tong,
Li Huayue,
Liu Zengzhi,
Dong Yujing,
Li Wenli
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202007777
Subject(s) - polyketide , acyl carrier protein , biosynthesis , polyketide synthase , biochemistry , thioester , polyene , moiety , isomerase , chemistry , stereochemistry , elongation factor , biology , gene , enzyme , rna , ribosome
As a unique structural moiety in natural products, cinnamoyl lipids (CLs), are proposed to be assembled by unusual type II polyketide synthases (PKSs). Herein, we demonstrate that the assembly of the CL compounds youssoufenes is accomplished by a PKS system that uniquely harbors three phylogenetically different ketosynthase/chain length factor (KS/CLF) complexes (YsfB/C, YsfD/E, and YsfJ/K). Through in vivo gene inactivation and in vitro reconstitution, as well as an intracellular tagged carrier‐protein tracking (ITCT) strategy developed in this study, we successfully elucidated the isomerase‐dependent ACP‐tethered polyunsaturated chain elongation process. The three KS/CLFs were revealed to modularly assemble different parts of the youssoufene skeleton, during which benzene ring closure happens right after the formation of an ACP‐tethered C18 polyene. Of note, the ITCT strategy could significantly contribute to the elucidation of other carrier‐protein‐dependent biosynthetic machineries.