真菌中 NRPS-NRPKS 杂合型聚酮合酶生物合成氨基酸衍生的α-吡喃酮。
Biosynthesis of Amino Acid Derived α-Pyrones by an NRPS-NRPKS Hybrid Megasynthetase in Fungi.
出版信息
J Nat Prod. 2020 Mar 27;83(3):593-600. doi: 10.1021/acs.jnatprod.9b00989. Epub 2020 Mar 11.
Abstract
A nonribosomal peptide synthetase (NRPS)-nonreducing polyketide synthase (NRPKS) hybrid enzyme (AnATPKS) from 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 -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.
摘要
来自 的非核糖体肽合成酶 (NRPS)-非还原性聚酮合酶 (NRPKS) 杂合酶 (AnATPKS) 被证明能够产生氨基酸衍生的 α-吡喃酮天然产物（吡喃酮和坎皮酮 B）。体外对 NRPS 模块的生化特性研究表明，该酶的氨酰化结构域对各种取代的苯丙氨酸类似物具有混杂性。利用前体喂养和 AnATPKS 及其相关的-O-甲基转移酶 (AnOMT) 的异源表达，我们能够获得一系列取代的吡喃酮类似物文库。我们的研究为使用 NRPS-NRPKS 杂合酶进行多样化的 α-吡喃酮天然产物的组合生物合成铺平了道路。
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2
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3
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4
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G3 (Bethesda). 2017 Jun 7;7(6):1791-1797. doi: 10.1534/g3.117.041384.
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