Phytochemicals are of great pharmaceutical and agricultural importance, but often exhibit low abundance in nature. Recent demonstrations of industrial-scale production of phytochemicals in yeast have shown that microbial production of these high-value chemicals is a promising alternative to sourcing these molecules from native plant hosts. However, a number of challenges remain in the broader application of this approach, including the limited knowledge of plant secondary metabolism and the inefficient reconstitution of plant metabolic pathways in microbial hosts. In this Review, we discuss recent strategies to achieve microbial biosynthesis of complex phytochemicals, including strategies to: (1) reconstruct plant biosynthetic pathways that have not been fully elucidated by mining enzymes from native and non-native hosts or by enzyme engineering; (2) enhance plant enzyme activity, specifically cytochrome P450 activity, by improving efficiency, selectivity, expression or electron transfer; and (3) enhance overall reaction efficiency of multi-enzyme pathways by dynamic control, compartmentalization or optimization with the host’s metabolism. We also highlight remaining challenges to — and future opportunities of — this approach.

植物化学物质在制药和农业方面具有重要意义，但自然界中的丰度通常较低。酵母在工业规模上生产植物化学药品的最新证明表明，这些高价值化学药品的微生物生产是从天然植物宿主中采购这些分子的有前途的替代方法。然而，在该方法的广泛应用中仍然存在许多挑战，包括对植物次生代谢的知识有限以及微生物宿主中植物代谢途径的低效重构。在这篇综述中，我们讨论了实现复杂植物化学物质微生物合成的最新策略，包括以下策略：（1）重建尚未从天然和非天然宿主中提取酶或通过酶工程方法充分阐明的植物生物合成途径; （2）通过提高效率，选择性，表达或电子转移来增强植物酶的活性，特别是细胞色素P450的活性；（3）通过动态控制，分隔或优化宿主代谢来提高多酶途径的整体反应效率。我们还将重点介绍这种方法所面临的挑战以及未来的机会。