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Structural and Biochemical Insight into the Recruitment of Acyl Carrier Protein‐Linked Extender Units in Ansamitocin Biosynthesis
Author(s) -
Zhang Fa,
Ji Huining,
Ali Imtiaz,
Deng Zixin,
Bai Linquan,
Zheng Jianting
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900628
Subject(s) - acyl carrier protein , polyketide , biosynthesis , acyltransferase , extender , biochemistry , acyltransferases , stereochemistry , polyketide synthase , biology , chemistry , enzyme , organic chemistry , polyurethane
A few acyltransferase (AT) domains of modular polyketide synthases (PKSs) recruit acyl carrier protein (ACP)‐linked extender units with unusual C2 substituents to confer functionalities that are not available in coenzyme A (CoA)‐linked ones. In this study, an AT specific for methoxymalonyl (MOM)‐ACP in the third module of the ansamitocin PKS was structurally and biochemically characterized. The AT uses a conserved tryptophan residue at the entrance of the substrate binding tunnel to discriminate between different carriers. A W275R mutation switches its carrier specificity from the ACP to the CoA molecule. The acyl‐AT complex structures clearly show that the MOM‐ACP accepted by the AT has the 2 S instead of the opposite 2 R stereochemistry that is predicted according to the biosynthetic derivation from a d ‐glycolytic intermediate. Together, these results reveal the structural basis of ATs recognizing ACP‐linked extender units in polyketide biosynthesis.