文献类型：期刊文献

英文题名：Gymnosperm-specific CYP90Js enable biflavonoid biosynthesis and microbial production of amentoflavone

作者：Dai, Xue-Hui[1,2,3];Zhu, Jiang-Ming[1,2,3];Wang, Guang-Yi[1,3];Ren, Yu-Hong[2];Liu, Hai-Li[1,2];Wang, Yong[1,2,3]

机构：[1]Chinese Acad Sci, Inst Plant Physiol & Ecol, CAS Ctr Excellence Mol Plant Sci, Lab Synthet Biol,State Key Lab Plant Trait Design, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[3]Univ Chinese Acad Sci, Beijing, Peoples R China

年份：2025

卷号：16

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001559618600008)】；

基金：This work is financially supported by the National Key R&D Program of China (No. 2024YFA0919900) to Y.W. and H.-L.L., the State Key Laboratory of Plant Trait Design to Y.W., the Key Laboratory of Plant Carbon Capture, Chinese Academy of Sciences to Y.W., and the Shanghai Municipal Science and Technology Major Project to Y.W. We thank Prof. David R. Nelson (University of Tennessee Health Science Center) for his assistance on the classification of the CYP90J subfamily referenced in this study.

语种：英文

摘要：Biflavonoids, a unique subclass of flavonoids with superior clinical activity compared to their monomeric counterparts, offer distinct therapeutic benefits by targeting multiple pathways in neurodegenerative disorders. However, the mechanism of flavonoid dimerization in plants remains enigmatic. Here, we identify CYP90J orthologs as the missing link in biflavonoid biosynthesis. We demonstrate that gymnosperm-specific CYP90Js catalyze intermolecular C-C bond formation in the biosynthesis of biaryl natural products. Together with the identified O-methyltransferases, CYP90Js are responsible for the production of ginkgo biflavonoids. Phylogenetic analysis reveals that the CYP90J subfamily evolved from CYP90E of lycophytes and is found exclusively in gymnosperms. Molecular dynamics simulations show that regioselective dimerization of apigenin to amentoflavone is driven by spatial constraints and pi-pi stacking interactions. QM/MM calculations support a heme-induced diradical coupling mechanism. Notably, the de novo reconstruction of amentoflavone was achieved in an engineered L-tyrosine E. coli strain, with a titer of 4.75 mg/L. Overall, the discovery of CYP90Js represents a crucial step toward understanding flavone dimerization, and the engineering of biflavonoids in microorganism provides a promising biotechnology platform for expanding therapeutic applications of biflavonoids.