Meng-Qi Yin , Kang Xu , Tao Luan , Xiu-Long Kang , Xiao-Yu Yang , Hong-Xing Li , Yun-Hua Hou , Jian-Zhi Zhao , Xiao-Ming Bao
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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 <em>S. cerevisiae</em>, 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). 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引用次数: 0
摘要
由于具有遗传可操作性和适宜的细胞内生理环境,酿酒酵母通常被用作生产高价值化合物或大宗化学品的微生物细胞工厂。目前,目标产品的生物合成途径主要是在细胞器内重新连接。然而,相关的前体、酶和辅助因子经常分布在不同的亚细胞区室,这可能会限制靶向化合物的生物合成。为了克服上述限制,生物合成途径被定位在不同的亚细胞器中进行产物生物合成。亚细胞区系化在靶向化合物的生产过程中具有多种优势,主要是可以缓解侧途径对前体的竞争,提高密闭空间的生物合成效率,以及减轻某些疏水性产物的细胞毒性。近年来,靶向化合物生物合成中的亚细胞区系化受到了广泛关注,并取得了令人满意的预期效果。在这篇综述中,我们总结了在 S. cerevisiae 中分区生物合成有价值化合物的最新进展,包括萜类、甾醇、生物碱、有机酸和脂肪醇等。此外,我们还介绍了不同细胞器在优化途径重建、辅助因子补充和关键前体(代谢物)合成的基础上,对特定化合物的特性和适用性。最后,我们讨论了通过亚细胞工程进行分区生物合成领域目前面临的挑战和策略,这将促进复杂的有价值化合物的生产,并为提高工业过程中产品的特异性和生产率提供潜在的解决方案。
Metabolic engineering for compartmentalized biosynthesis of the valuable compounds in Saccharomyces cerevisiae
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.
期刊介绍:
Microbiological Research is devoted to publishing reports on prokaryotic and eukaryotic microorganisms such as yeasts, fungi, bacteria, archaea, and protozoa. Research on interactions between pathogenic microorganisms and their environment or hosts are also covered.