酿酒酵母由于其遗传可操作性和合适的细胞内生理环境,通常被用作微生物细胞工厂来生产高价值的化合物或散装化学品。目前靶向产物的生物合成途径主要在胞质区室中重新连接。然而,相关的前体,酶,辅因子经常分布在不同的亚细胞区室,这可能会限制目标化合物的生物合成。为了克服上述限制,生物合成途径位于产品生物合成的不同亚细胞器中。在目标化合物的生产中的亚细胞区室化提供了几个优点,主要是缓解从侧面途径对前体的竞争,提高密闭空间中的生物合成效率,并减轻某些疏水产物的细胞毒性。近年来,在靶向化合物生物合成中的亚细胞区室化受到了广泛的关注,并达到了令人满意的期望。在这次审查中,我们总结了酿酒酵母中有价值化合物的分区生物合成的最新进展,包括萜类化合物,固醇,生物碱,有机酸,和脂肪醇,等。此外,我们描述了不同细胞器对特定化合物的特征和适用性,基于路径重建的优化,辅因子补充,以及关键前体(代谢物)的合成。最后,我们讨论了当前的挑战和战略领域的分区生物合成通过亚细胞工程,这将促进复杂的有价值的化合物的生产,并提供潜在的解决方案,以提高工业过程中的产品特异性和生产率。
Saccharomyces cerevisiae is commonly used as a microbial cell factory to produce high-value compounds or bulk chemicals due to its genetic operability and suitable intracellular physiological environment. The current biosynthesis pathway for targeted products is primarily rewired in the cytosolic compartment. However, the related precursors, enzymes, and cofactors are frequently distributed in various subcellular compartments, which may limit targeted compounds biosynthesis. To overcome above mentioned limitations, the biosynthesis pathways are localized in different subcellular organelles for product biosynthesis. Subcellular compartmentalization in the production of targeted compounds offers several advantages, mainly relieving competition for precursors from side pathways, improving biosynthesis efficiency in confined spaces, and alleviating the cytotoxicity of certain hydrophobic products. In recent years, subcellular compartmentalization in targeted compound biosynthesis has received extensive attention and has met satisfactory expectations. In this review, we summarize the recent advances in the compartmentalized biosynthesis of the valuable compounds in S. cerevisiae, including terpenoids, sterols, alkaloids, organic acids, and fatty alcohols, etc. Additionally, we describe the characteristics and suitability of different organelles for specific compounds, based on the optimization of pathway reconstruction, cofactor supplementation, and the synthesis of key precursors (metabolites). Finally, we discuss the current challenges and strategies in the field of compartmentalized biosynthesis through subcellular engineering, which will facilitate the production of the complex valuable compounds and offer potential solutions to improve product specificity and productivity in industrial processes.