A cinnamyl alcohol dehydrogenase–like scaffold organizes monoterpenoid indole alkaloid biosynthesis
Year: 2026
Type: article
Abstract: Biosynthesis of ~3000 monoterpenoid indole alkaloids (MIAs), including the anticancer drug vinblastine, involves the highly unstable intermediate strictosidine aglycone. Its formation by strictosidine β-glucosidase (SGD) and subsequent conversion by geissoschizine synthase (GS) occur in spatially separated compartments, representing a major biosynthesis bottleneck. In this study, we discover VinBLAST, a cinnamyl alcohol dehydrogenase-like protein repurposed as a scaffold for efficient processing of this labile intermediate. VinBLAST physically mediates the interaction of SGD and GS in the nucleus and allosterically enhances the catalytic efficiency of GS. VinBLAST homologs from diverse plant families enhance the biosynthesis of several representative MIAs, with the production of catharanthine increased to ~160 milligrams per liter in yeast, nearly 1000-fold higher than shown in previous studies. Our discovery provides a missing link in organizing MIA biosynthesis and enables scalable bioproduction of geissoschizine-derived therapeutics.
Source: Science
Authors: Di Gao, Scott Galeung Alexander Mann, Binbin Chen, Yuanwei Gou, Cong Chen, Chong Qiao, Jorge Jonathan Oswaldo Garza-Garcia, Mohammadamin Shahsavarani, Xiaojing Jiang, Hannah Caroline Tran, Jingfei Bao, Mathew Bailey Richardson, Jianing Li, Jacob Owen Perley, Jaewook Hwang, Feng Dong, Chang Dong, Lei Huang, Vincenzo De Luca, Yajie Wang, Yang Qu, Jiazhang Lian
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7169208223