Allantofuranone Biosynthesis and Precursor-Directed Mutasynthesis of Hydroxylated Analogues.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-05-23 Epub Date: 2025-04-18 DOI:10.1021/acs.jnatprod.5c00197

Carsten Wieder, Claudia Simon-Sánchez, Johannes C Liermann, Rainer Wiechert, Karsten Andresen, Eckhard Thines, Till Opatz, Anja Schüffler

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Abstract

Genome mining and heterologous reconstitution of biosynthetic genes in Aspergillus oryzae enabled elucidation of the hitherto elusive biosynthetic route that produces allantofuranone (1), a bioactive natural product originally isolated from Allantophomopsis lycopodina. The core non-ribosomal peptide synthetase (NRPS)-like enzyme AlfA of the alf BGC produces polyporic acid (2) from phenylpyruvic acid. In subsequent reactions, compound 2 is reductively dehydrated by the bifunctional enzyme AlfC and methylated by AlfD to produce terferol (6). In a final step, the quinol moiety of compound 6 is oxidatively cleaved and contracted by the aromatic ring cleavage dioxygenase AlfB. Using combinatorial biosynthesis, we were able to manipulate the biosynthetic route to yield hydroxylated pathway congeners, most notably the new natural products deoxyascocorynin (10), hydroxyterferol (11), and hydroxyallantofuranone (12).

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尿囊呋喃酮生物合成及羟基化类似物前体定向突变合成。

基因组挖掘和米曲霉生物合成基因的异源重组使得迄今为止难以捉摸的产生尿囊呋喃酮的生物合成途径得以阐明(1)，尿囊呋喃酮是一种生物活性天然产物，最初从石芋毛霉中分离出来。半BGC的核心非核糖体肽合成酶（NRPS）样酶AlfA从苯基丙酮酸产生聚磷酸(2)。在随后的反应中，化合物2被双功能酶AlfC还原脱水，并被AlfD甲基化生成terferol(6)。在最后一步，化合物6的喹啉部分被芳环裂解双加氧酶AlfB氧化裂解并收缩。使用组合生物合成，我们能够操纵生物合成路线以产生羟基化途径同系物，最显著的是新的天然产物脱氧抗坏血酸（10），羟基terferol（11）和羟基尿囊呋喃酮（12）。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.