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

Yang Hai | Zendy; Arthur Huang | Zendy; Yi Tang | Zendy

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

Author(s) -

Yang Hai,

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.

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