Work

Methylation-Dependent Acyl Transfer between Polyketide Synthase and Nonribosomal Peptide Synthetase Modules in Fungal Natural Product Biosynthesis

Year: 2014

Type: article

Abstract: Biochemical studies of purified and dissected fungal polyketide synthase and nonribosomal peptide synthetase (PKS-NRPS) hybrid enzymes involved in biosynthesis of pseurotin and aspyridone indicate that one α-methylation step during polyketide synthesis is a prerequisite and a key checkpoint for chain transfer between PKS and NRPS modules. In the absence of the resulting γ-methyl feature, the completed polyketide intermediate is offloaded as an α-pyrone instead of being aminoacylated by the NRPS domain. These examples illustrate that precisely timed tailoring domain activities play critical roles in the overall programming of the iterative PKS (and NRPS) functions.

Source: Organic Letters

DOI: 10.1021/ol503179v

Authors: Yi Zou, Wei Xu, Yuta Tsunematsu, Mancheng Tang, Kenji Watanabe, Yi Tang

Institutions: University of California, Los Angeles, Shizuoka University, University of Shizuoka

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $4,500