Efficient biosynthesis of heterodimeric C3-aryl pyrroloindoline alkaloids

• DOI: 10.1038/s41467-018-06528-z
• Publication Date: 2018-10-18T15:57:50Z
• Authors: Wenya Tian; Chenghai Sun; Mei Zheng; Jeffrey R. Harmer; Mingjia Yu; Yanan Zhang; Haidong Peng; Dongqing Zhu; Zixin Deng; Shi-Lu Chen; Mehdi Mobli; Xinying Jia; Xudong Qu
• Keywords: Synthetic Biology

Abstract Many natural products contain the hexahydropyrrolo[2, 3- b ]indole (HPI) framework. HPI containing chemicals exhibit various biological activities and distinguishable structural arrangement. This complexity renders chemical synthesis very challenging. Here, through investigating biosynthesis of a naturally occurring C 3 -aryl HPI, naseseazine (NAS-C), we identify P450 enzyme (NascB) reveal that NascB catalyzes radical cascade reaction to form intramolecular intermolecular carbon–carbon bonds with both regio- stereo-specificity. Surprisingly, limited freedom is allowed in specificity generate four types scaffolds, two them were not previously observed. By incorporating into an engineered strain E. coli , develop whole-cell biocatalysis system for efficient production NAS-C 30 NAS analogs. Interestingly, find some these analogs potent neuroprotective properties. Thus, our biocatalytic methodology offers simple route difficult framework chemicals.