期刊
JOURNAL OF NATURAL PRODUCTS
卷 83, 期 3, 页码 593-600出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.9b00989
关键词
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资金
- NIH [1R35GM118056]
- Mark Foundation for Cancer Research
- Lorraine H. and Masuo Toji Summer Research fellowship
A nonribosomal peptide synthetase (NRPS)-nonreducing polyketide synthase (NRPKS) hybrid enzyme (AnATPKS) from Aspergillus niger was shown to produce amino acid derived alpha-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 alpha-pyrone natural products using NRPS-NRPKS hybrids.
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