近日，浙江大学连佳长团队报道了肉桂醇脱氢酶样支架组织单萜类吲哚生物碱的生物合成。相关论文于2026年8月20日发表在《科学》杂志上。

约3000种单萜吲哚生物碱（MIAs）的生物合成，包括抗癌药物长春碱在内，涉及高度不稳定的中间体异胡豆苷苷元。该中间体由异胡豆苷β-葡萄糖苷酶（SGD）生成，并随后由吉索希钦合酶（GS）转化，这两个过程发生在空间上分隔的细胞区室中，构成了生物合成的一个主要瓶颈。

研究组发现VinBLAST能够高效处理这一不稳定中间体，VinBLAST是一种被重新利用为支架蛋白的肉桂醇脱氢酶类似蛋白。VinBLAST在细胞核中物理介导SGD与GS的相互作用，并通过别构效应增强GS的催化效率。来自不同植物科的VinBLAST同源蛋白能够增强数种代表性MIAs的生物合成，其中长春质碱在酵母中的产量提升至约160毫克/升，较此前研究所示提高了近1000倍。该发现填补了MIA生物合成组织化过程中的一个缺失环节，并为吉索希钦衍生治疗药物的规模化生物生产奠定了基础。

附：英文原文

Title: A cinnamyl alcohol dehydrogenase–like scaffold organizes monoterpenoid indole alkaloid biosynthesis

Author: Scott Galeung Alexander Mann, Jorge Jonathan Oswaldo Garza-Garcia, Hannah Caroline Tran, Mathew Bailey Richardson, Jacob Owen Perley, Vincenzo De Luca

Issue&Volume: 2026-08-20

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.

DOI: aeb0357

Source: https://www.science.org/doi/10.1126/science.aeb0357