萜类高效合成平台的搭建与萜类产物批量挖掘
程 术,邓子新,卞光凯,刘天罡*
(武汉大学药学院,组合生物合成及新药发现教育部重点实验室,武汉 430071)

摘 要:摘 要:萜类化合物是天然产物中的重要类群,其结构多样性赋予这类化合物广泛的用途,如抗疟疾的青蒿素、抗乳腺癌的紫杉醇、抗氧化的番茄红素、天然名贵香料檀香油、航空燃油前体化合物法尼烯等。这些高价值萜类化合物的大量生产和新型萜类化合物的高效挖掘是代谢工程和天然产物挖掘领域的主要挑战。定向合成代谢、体外重组策略和组学研究指导下的理性代谢工程改造,优化了宿主平衡代谢通路,加快了高价值萜类产物的发现历程。现综述了近年来萜类化合物代谢工程改造和基因组挖掘的研究策略,并展望了萜类化合物挖掘的途径以及在真菌体内的异源表达和代谢工程改造。

Construction of high-efficient terpenoid platform and the application in terpenoid discovery
CHENG Shu, DENG Zi-Xin, BIAN Guang-Kai, LIU Tian-Gang*
(Key Laboratory of Combinational Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China)

Abstract: Abstract: Terpenoids are important components of natural products. Their structural diversity endows it with extensive applications, such as antimalarial artemisinin, anticancer paclitaxel, antioxidative lycopene, natural and precious spices sandalwood oil, and jet fuel precursor farnesene. The overproduction of high-value terpenoids and the efficient mining of new terpenes are the major challenges in the field of metabolic engineering and natural products discovery. Target synthetic metabolism, in vitro reconstitution strategy and rational metabolic engineering under the guidance of omics studies can optimize host and balance metabolic pathways, accelerate the discovery process of high-value terpenoids. The strategies of metabolic engineering and genome mining of the terpenoids in recent years were reviewed in this article. Furthermore, the discovery of the terpenoids, heterologous expression in fungi and the metabolic engineering in fungi were prospected.

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