长春花碱已在临床上用作治疗多种癌症的最有效的疗法之一。然而，传统的植物提取方法存在供应不可靠、丰度低、成本极高的问题。在这里，我们使用合成生物学方法对酿酒酵母进行改造，以从头生物合成长春花碱和长春花碱，它们可以通过化学或生物方式与长春花碱偶联。在具有充足的生物合成前体和辅因子供应的平台菌株的基础上，我们重构、消除了瓶颈并优化了文多灵和长春质的生物合成途径。文多灵生物合成途径是微生物细胞工厂中迄今为止重建的最复杂的途径之一。通过摇瓶发酵，我们的工程酵母菌株能够分别以 527.1 和 305.1 μg·liter-1 的滴度生产长春质和文多灵，且不会积累可检测量的途径中间体。这项研究为在酵母中生产有价值的植物天然产物建立了一个代表性的例子。版权所有 © 2022 Di Gaut al.

Vinblastine has been used clinically as one of the most potent therapeutics for the treatment of several types of cancer. However, the traditional plant extraction method suffers from unreliable supply, low abundance, and extremely high cost. Here, we use synthetic biology approach to engineer Saccharomyces cerevisiae for de novo biosynthesis of vindoline and catharanthine, which can be coupled chemically or biologically to vinblastine. On the basis of a platform strain with sufficient supply of precursors and cofactors for biosynthesis, we reconstituted, debottlenecked, and optimized the biosynthetic pathways for the production of vindoline and catharanthine. The vindoline biosynthetic pathway represents one of the most complicated pathways ever reconstituted in microbial cell factories. Using shake flask fermentation, our engineered yeast strains were able to produce catharanthine and vindoline at a titer of 527.1 and 305.1 μg·liter-1, respectively, without accumulating detectable amount of pathway intermediates. This study establishes a representative example for the production of valuable plant natural products in yeast.Copyright © 2022 Di Gao et al.