Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite  

作　　者：Zhiguo Liu Wei Li Peng Zhang Jie Fan Fangbo Zhang Caixia Wang Shuming Li Yi Sun Shilin Chen Wenbing Yin 

机构地区：[1]Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China [2]State Key Laboratory of Mycology,CAS Key Laboratory of Microbial Physiological and Metabolic Engineering,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China [3]Savaid Medical School,University of Chinese Academy of Sciences,Beijing 100049,China [4]Institut für Pharmazeutische Biologie und Biotechnologie,Fachbereich Pharmazie,Philipps-Universitat Marburg,Marburg 35037,Germany

出　　处：《Acta Pharmaceutica Sinica B》2021年第11期3655-3664,共10页药学学报（英文版）

基　　金：supported in part by National Key Research and Development Program of China(2020YFA0907800 and 2018YFC1706104);National Natural Science Foundation of China(31861133004 and 81502968);the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation Li844/11-1,Germany);Key Research Program of Frontier Sciences,CAS(ZDBS-LY-SM016,China)。

摘　　要：Tyrosine-decahydrofluorene derivatives feature a fused[6.5.6]tricarbocyclic core and a 13-membered para-cyclophane ether.Herein,we identified new xenoacremones A,B,and C(1-3)from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans.The hybrid polyketide synthaseenonribosomal peptide synthetase(PKS-NRPS)XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton.This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety.XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system.Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether,which underwent subsequent spontaneous Diels-Alder reaction to give the end products.Thus,the results indicated that three novel enzymes XenF,XenD,and XenC coordinate to assemble the[6.5.6]tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.

关 键 词：Tyrosine-decahydrofluorene BIOSYNTHESIS PKS-NRPS Xenoacremone Heterologous expression 

分 类 号：O621.25[理学—有机化学]