A Long‐Range Acting Dehydratase Domain as the Missing Link for C17‐Dehydration in Iso‐Migrastatin Biosynthesis. (19th May 2017)

• Record Type: Journal Article
• Authors: Zhang, Bo; Xu, Zhengren; Teng, Qihui; Pan, Guohui; Ma, Ming; Shen, Ben
• Is Part Of: Angewandte Chemie. Volume 129:Number 25(2017)
• Page Start: 7353
• Page End: 7357
• Publication Date: 2017-05-19
• Subjects: Biosynthese -- Dehydratase -- Isomigrastatin -- Naturstoffe -- Polyketide; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201703588
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The dehydratase domains (DHs) of the iso‐migrastatin (iso‐MGS) polyketide synthase (PKS) were investigated by systematic inactivation of the DHs in module‐6, ‐9, ‐10 of MgsF (i.e., DH6, DH9, DH10) and module‐11 of MgsG (i.e., DH11) in vivo, followed by structural characterization of the metabolites accumulated by the mutants, and biochemical characterization of DH10 in vitro, using polyketide substrate mimics with varying chain lengths. These studies allowed us to assign the functions for all four DHs, identifying DH10 as the dedicated dehydratase that catalyzes the dehydration of the C17 hydroxy group during iso‐MGS biosynthesis. In contrast to canonical DHs that catalyze dehydration of the β‐hydroxy groups of the nascent polyketide intermediates, DH10 acts in a long‐range manner that is unprecedented for type I PKSs, a novel dehydration mechanism that could be exploited for polyketide structural diversity by combinatorial biosynthesis and synthetic biology.