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Engineered Biosynthesis of 5/5/6 Type Polycyclic Tetramate Macrolactams in an Ikarugamycin (5/6/5 Type)-Producing Chassis

Hong-Bo Jin, Wenjun Zhang, Guangtao Zhang, Liping Zhang, Wei Liu, Changsheng Zhang

2020Organic Letters26 citationsDOI

Abstract

Combinatorial biosynthesis of 5/5/6 type polycyclic tetramate macrolactams (PoTeMs) was achieved in an engineered ikarugamycin (5/6/5 type) producer by introducing a set of 5/5/6 type PoTeM biosynthetic genes from Streptomyces griseus. This study supports the idea that PoTeMs share a common polyene tetramate precursor generated by the hybrid polyketide synthase/nonribosomal peptide synthetase enzymes. The X-ray crystal structure of pactamide G (7) sets an example for resolving the absolute configuration of 5/5/6 type PoTeMs.

Topics & Concepts

BiosynthesisNonribosomal peptideChemistryPolyenePolyketide synthasePolyketideStreptomyces griseusStereochemistryStreptomycesType (biology)EnzymeBiochemistryBiologyGeneticsBacteriaEcologyMicrobial Natural Products and BiosynthesisEnzyme Production and CharacterizationChemical Synthesis and Analysis
Engineered Biosynthesis of 5/5/6 Type Polycyclic Tetramate Macrolactams in an Ikarugamycin (5/6/5 Type)-Producing Chassis | Litcius