Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining
Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining
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通过基因组挖掘发现真菌中独特的类黄酮生物合成机制
DOI：
10.1002/anie.202215529
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Xuefeng Lu
中科院分区：
文献类型：
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作者：
Wei Zhang;Xuan Zhang;D;an Feng;Yajing Liang;Zhenying Wu;Siyu Du;Yu Zhou;Ce Geng;Ping Men;Chunxiang Fu;Xuenian Huang;Xuefeng Lu
黄酮类化合物是一类重要的植物天然产物，具有多种结构和生物活性。所有已知的植物类黄酮都是在III型聚酮化合物合酶（PKS），随后是查耳酮异构酶（CHI）和黄酮合酶（FNS）的催化下产生的。 在这项研究中，chlorflavonin的生物合成基因簇，一种具有乙酰乳酸合成酶抑制活性的真菌类黄酮，使用自我抗性基因导向策略发现。揭示了一条新的真菌类黄酮生物合成途径。核心非核糖体肽合成酶-聚酮合酶（NRPS-PKS）负责关键前体查耳酮的产生。然后，一种新型的CHI通过组氨酸介导的oxa-Michael加成机制催化查尔酮转化为黄烷酮。最后，黄烷酮去饱和成黄酮是由一种新型的FNS催化的，FNS是一种黄素单苷脂（FMN）依赖性氧化还原酶。
Flavonoids are important plant natural products with variable structures and bioactivities. All known plant flavonoids are generated under the catalysis of a type III polyketide synthase (PKS) followed by a chalcone isomerase (CHI) and a flavone synthase (FNS). In this study, the biosynthetic gene cluster of chlorflavonin, a fungal flavonoid with acetolactate synthase inhibitory activity, was discovered using a self‐resistance‐gene‐directed strategy. A novel flavonoid biosynthetic pathway in fungi was revealed. A core nonribosomal peptide synthetase‐polyketide synthase (NRPS‐PKS) is responsible for the generation of the key precursor chalcone. Then, a new type of CHI catalyzes the conversion of a chalcone into a flavanone by a histidine‐mediated oxa‐Michael addition mechanism. Finally, the desaturation of flavanone to flavone is catalyzed by a new type of FNS, a flavin mononucleotide (FMN)‐dependent oxidoreductase.