Biosynthesis of Amino Acid Derived α-Pyrones by an NRPS-NRPKS Hybrid Megasynthetase in Fungi.

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Biosynthesis of Amino Acid Derived α-Pyrones by an NRPS-NRPKS Hybrid Megasynthetase in Fungi.

J Nat Prod. 2020 Mar 11;:

Authors: Hai Y, Huang A, Tang Y

Abstract
A nonribosomal peptide synthetase (NRPS)-nonreducing polyketide synthase (NRPKS) hybrid enzyme (AnATPKS) from Aspergillus niger was shown to produce amino acid derived α-pyrone natural products (pyrophen and campyrone B). Biochemical characterization of the NRPS module in vitro reveals that the adenylation domain is promiscuous toward a variety of substituted phenylalanine analogues. Using precursor feeding and heterologous expression of AnATPKS and an associated O-methyltransferase (AnOMT), we were able to access a library of substituted pyrophen analogues. Our study paves the way for future combinatorial biosynthesis of diverse α-pyrone natural products using NRPS-NRPKS hybrids.

PMID: 32159958 [PubMed – as supplied by publisher]

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