非常规酵母的分子遗传学及合成生物学研究进展

Advances in molecular genetics and synthetic biology tools in unconventional yeasts

摘要:

先进的合成生物学技术与传统的分子遗传学技术的结合更有助于实现酵母底盘细胞的快速改造和优化。酵母合成生物学研究最早开始于常规酵母——酿酒酵母（Saccharomyces cerevisiae），近些年来又迅速扩展至一些非常规酵母，包括巴斯德毕赤酵母（Pichia pastoris）、解脂耶氏酵母（Yarrowia lipolytica）、乳酸克鲁维酵母（Kluyveromyces lactis）和多形汉逊酵母（Hansenula polymorpha）等。借助合成生物学技术与工具，目前科学家们已经成功开发出了能够高效生产生物材料、生物燃料、生物基化学品、蛋白质制剂、食品添加剂和药物等工业产品的重组非常规酵母工程菌株。本文系统总结了合成生物学工具（主要是基因组编辑工具）、合成生物学组件（主要是启动子和终止子）和相关分子遗传学方法在上述非常规酵母系统（底盘细胞）中的最新研究进展和应用情况，并讨论了其他合成生物学技术在这些非常规酵母表达系统中的潜在适用性和应用前景。这为研究人员利用合成生物学方法在这一新型非模式微生物底盘细胞中设计和构建各种高附加值工业产品的异源合成模块并最终实现目标化合物的高效生物合成提供了科学的理论指导。

Abstract:

Currently, it is widely accepted that the combination of advanced synthetic biology techniques with traditional molecular genetic techniques could help construct and optimize metabolic pathways in yeast cell factories. The research of yeast synthetic biology first began in the model yeast Saccharomyces cerevisiae, and in recent years has rapidly expanded to some unconventional yeast species including Pichia pastoris, Yarrowia lipolytica, Kluyveromyces lactis, and Hansenula polymorpha. By using synthetic biology-based metabolic engineering strategies, scientists have successfully developed a series of unconventional yeast cell factories that can efficiently produce different valuable industrial products such as biomaterials, biofuels, biochemicals, enzymes, food additives and pharmaceuticals. This review systematically summarizes the current status and applications of synthetic biology tools (mainly genome editing tools), synthetic biological parts (mainly promoters and terminators) and related molecular genetic methods in the aforementioned unconventional yeast systems. Furthermore, potential applications of other synthetic biology approaches in further optimizing bioproduction in the unconventional yeast biofactories and key challenges are discussed. This review provides a theoretical guidance for engineering these promising non-model microbial chassis to achieve high-level production of value-added products.