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


ABSTRACT: A nonribosomal peptide synthetase (NRPS)-nonreducing polyketide synthase (NRPKS) hybrid enzyme (AnATPKS) from Aspergillus niger was shown to produce amino acid derived ?-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 ?-pyrone natural products using NRPS-NRPKS hybrids.

SUBMITTER: Hai Y 

PROVIDER: S-EPMC7166049 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Hai Yang Y   Huang Arthur A   Tang Yi Y  

Journal of natural products 20200311 3


A nonribosomal peptide synthetase (NRPS)-nonreducing polyketide synthase (NRPKS) hybrid enzyme (AnATPKS) from <i>Aspergillus niger</i> 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 <i>O</i>-methyltransferas  ...[more]

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