Open AccessBiosynthesis of Amino Acid Derived α-Pyrones by an NRPS–NRPKS Hybrid Megasynthetase in Fungi
Author(s) -
Hai Yan,
Arthur Huang,
Yi Tang
Publication year - 2020
Publication title -
journal of natural products
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 139
eISSN - 1520-6025
pISSN - 0163-3864
DOI - 10.1021/acs.jnatprod.9b00989
Subject(s) - nonribosomal peptide , biosynthesis , adenylylation , polyketide , polyketide synthase , pyrone , heterologous expression , amino acid , biochemistry , enzyme , biology , stereochemistry , chemistry , recombinant dna , gene
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.