A Long‐Range Acting Dehydratase Domain as the Missing Link for C17‐Dehydration in Iso‐Migrastatin Biosynthesis

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.

A Zinc Cobalt Sulfide Nanosheet Array Derived from a 2D Bimetallic Metal–Organic Frameworks for High‐Performance Supercapacitors

“…Furthermore, the electrochemical performance of the as‐prepared Zn‐Co‐S/NF compares favourably with those of other metal sulfide electrodes (Table S1 in the Supporting Information). For instance, the specific capacitance of Zn‐Co‐S/NF is higher than those of, for example, Zn 0.76 Co 0.24 S nanoartichokes (486.2 F g −1 at 2 A g −1 ), double‐shelled zinc cobalt sulfide rhombic dodecahedral cages (1266 F g −1 at 1 A g −1 ), mesoporous NiCo 2 S 4 polyhedra (1296 F g −1 at 1 A g −1 ) and 3D honeycomb‐like NiCo 2 S 4 (1168 F g −1 at 1 A g −1 ) …”

“…Bimetallic MOFs with homogeneous distributions of two kinds of metal nodes could be utilized as ideal templates to construct bimetallic sulfides with controllable composition . Nevertheless, reports on the design of bimetallic sulfides directly from bimetallic MOF precursors are scarce . Furthermore, the reported MOF derivatives are mainly nanocages and nancubes.…”

Tuning Metallic Co0.85Se Quantum Dots/Carbon Hollow Polyhedrons with Tertiary Hierarchical Structure for High-Performance Potassium Ion Batteries

“…Therefore, controlling the uniform dispersion of nanoparticles in hierarchical structure becomes the focus of researches. Generally, the metal organic frameworks (MOFs) structure can meet the above requirements [29][30][31]. QDs, carbon matrix, and hierarchical structure can be obtained by further processing different MOFs.…”

Loss of Single‐Domain Function in a Modular Assembly Line Alters the Size and Shape of a Complex Polyketide

“…The formation of 2 can be explained by the non‐quantitative reduction of the β‐keto group in module 2 as observed in the wild‐type PKS ( S. albus ::pHJ48). Traces of 1 in the DH2 null mutant can be explained by non‐enzymatic dehydration of the hydroxy intermediate, or by the involvement of a long‐range acting DH domain as in iso‐migrastatin biosynthesis …”