Harnessing the yeast Saccharomyces cerevisiae for the production of fungal secondary metabolites.
Harnessing the yeast Saccharomyces cerevisiae for the production of fungal secondary metabolites.
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DOI：
10.1042/ebc20200137
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发表时间：
2021-07-26
影响因子：
6.4
通讯作者：
Borodina I
中科院分区：
文献类型：
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作者：
Wang G;Kell DB;Borodina I
真菌次生代谢物（FSMs）代表了一系列显著的生物活性化合物，在药物、营养药品和农用化学品方面具有潜在的应用。然而，这些分子通常只能由它们的原生宿主产生有限的数量。本土生物也可能难以培育和基因工程，有些可能产生不受欢迎的有毒副产品。另外，真菌生物活性的重组生产可以被设计成工业细胞工厂，如曲霉或酵母，它们很适合大规模的水下发酵生产。本文综述了面包酵母（Saccharomyces cerevisiae）从丝状真菌和蘑菇中提取化合物的研究进展。这些化合物主要包括聚酮类、萜类和氨基酸衍生物。我们还描述了原生生物合成途径如何结合或扩展以产生新的衍生物和新的天然化合物。我们描述了一些细胞工厂工程的新方法，如基因组规模工程、基于生物传感器的高通量筛选和机器学习，以及如何将这些工具应用于酿酒葡萄球菌菌株改良。最后，我们展望了酵母细胞工厂进一步发展的挑战和解决方案，以更有效地生产fsm。
Fungal secondary metabolites (FSMs) represent a remarkable array of bioactive compounds, with potential applications as pharmaceuticals, nutraceuticals, and agrochemicals. However, these molecules are typically produced only in limited amounts by their native hosts. The native organisms may also be difficult to cultivate and genetically engineer, and some can produce undesirable toxic side-products. Alternatively, recombinant production of fungal bioactives can be engineered into industrial cell factories, such as aspergilli or yeasts, which are well amenable for large-scale manufacturing in submerged fermentations. In this review, we summarize the development of baker’s yeast Saccharomyces cerevisiae to produce compounds derived from filamentous fungi and mushrooms. These compounds mainly include polyketides, terpenoids, and amino acid derivatives. We also describe how native biosynthetic pathways can be combined or expanded to produce novel derivatives and new-to-nature compounds. We describe some new approaches for cell factory engineering, such as genome-scale engineering, biosensor-based high-throughput screening, and machine learning, and how these tools have been applied for S. cerevisiae strain improvement. Finally, we prospect the challenges and solutions in further development of yeast cell factories to more efficiently produce FSMs.