Discovery of a Unique Flavonoid Biosynthesis Mechanism in Fungi by Genome Mining

作者：Wei Zhang, Xuan Zhang, Dandan Feng, Yajing Liang, Zhenying Wu, Siyu Du, Yu Zhou, Ce Geng, Ping Men, Chunxiang Fu, Xuenian Huang, Xuefeng Lü · 发表于：Angewandte Chemie International Edition · 年份：2023 · DOI：10.1002/anie.202215529 · 被引用次数：39 · 研究领域：Microbial Natural Products and Biosynthesis、Plant biochemistry and biosynthesis、Plant Gene Expression Analysis

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.