Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Gothenburg, Sweden.
Methods Mol Biol. 2022;2489:333-367. doi: 10.1007/978-1-0716-2273-5_18.
Cell factories can provide a sustainable supply of natural products with applications as pharmaceuticals, food-additives or biofuels. Besides being an important model organism for eukaryotic systems, Saccharomyces cerevisiae is used as a chassis for the heterologous production of natural products. Its success as a cell factory can be attributed to the vast knowledge accumulated over decades of research, its overall ease of engineering and its robustness. Many methods and toolkits have been developed by the yeast metabolic engineering community with the aim of simplifying and accelerating the engineering process.In this chapter, a range of methodologies are highlighted, which can be used to develop novel natural product cell factories or to improve titer, rate and yields of an existing cell factory with the goal of developing an industrially relevant strain. The addressed topics are applicable for different stages of a cell factory engineering project and include the choice of a natural product platform strain, expression cassette design for heterologous or native genes, basic and advanced genetic engineering strategies, and library screening methods using biosensors. The many engineering methods available and the examples of yeast cell factories underline the importance and future potential of this host for industrial production of natural products.
细胞工厂可以为天然产物的可持续供应提供支持，这些天然产物可应用于制药、食品添加剂或生物燃料等领域。除了是真核系统的重要模式生物外，酿酒酵母还被用作异源生产天然产物的底盘。它之所以能够成为一个成功的细胞工厂，可以归因于几十年来积累的大量知识、其整体易于工程化设计以及其稳健性。酵母代谢工程界已经开发出许多方法和工具包，旨在简化和加速工程化进程。在本章中，强调了一系列方法，这些方法可用于开发新型天然产物细胞工厂，或提高现有细胞工厂的产量、速率和产率，以开发出具有工业相关性的菌株。所涉及的主题适用于细胞工厂工程化项目的不同阶段，包括天然产物平台菌株的选择、异源或内源基因的表达盒设计、基本和高级遗传工程策略，以及使用生物传感器的文库筛选方法。可用的许多工程方法和酵母细胞工厂的例子突出了该宿主在天然产物工业生产中的重要性和未来潜力。
