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构建用于萜类化合物合成的非模式酵母。

Engineering a non-model yeast for terpenoids synthesis.

作者信息

Chen Qiongqiong, Lyu Liting, Xue Haizhao, Shah Aabid Manzoor, Zhao Zongbao Kent

机构信息

Laboratory of Biotechnology, Dalian Institute of Chemical Physics, CAS, 457 Zhongshan Road, Dalian, 116023, China.

University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China.

出版信息

Synth Syst Biotechnol. 2024 Apr 23;9(3):569-576. doi: 10.1016/j.synbio.2024.04.015. eCollection 2024 Sep.

Abstract

Terpenoids have tremendous biological activities and are widely employed in food, healthcare and pharmaceutical industries. Using synthetic biology to product terpenoids from microbial cell factories presents a promising alternative route compared to conventional methods such as chemical synthesis or phytoextraction. The red yeast has been widely studied due to its natural production capacity of carotenoid and lipids, indicating a strong endogenous isoprene pathway with readily available metabolic intermediates. This study constructed several engineered strains of with the aim of producing different terpenoids. Monoterpene α-terpineol was produced by expressing the α-terpineol synthase from . The titer of α-terpineol was further enhanced to 0.39 mg/L by overexpressing the endogenous rate-limiting gene of the MVA pathway. Overexpression of α-farnesene synthase from in combination with MVA pathway rate-limiting gene resulted in significant increase in α-farnesene production, reaching a titer of 822 mg/L. The carotenoid degradation product β-ionone was produced at a titer of 0.87 mg/L by expressing the β-ionone synthase from . This study demonstrates the potential of as a platform host for the direct biosynthesis of various terpenoids and provides insights for further development of such platforms.

摘要

萜类化合物具有巨大的生物活性,广泛应用于食品、医疗保健和制药行业。与化学合成或植物提取等传统方法相比,利用合成生物学从微生物细胞工厂生产萜类化合物提供了一条有前景的替代途径。红酵母由于其天然的类胡萝卜素和脂质生产能力而受到广泛研究,这表明其具有强大的内源性异戊二烯途径和易于获得的代谢中间体。本研究构建了几种工程菌株,旨在生产不同的萜类化合物。通过表达来自[具体来源]的α-萜品醇合酶来生产单萜α-萜品醇。通过过表达MVA途径的内源性限速基因,α-萜品醇的产量进一步提高到0.39mg/L。来自[具体来源]的α-法呢烯合酶与MVA途径限速基因的过表达相结合,导致α-法呢烯产量显著增加,达到822mg/L的产量。通过表达来自[具体来源]的β-紫罗兰酮合酶,类胡萝卜素降解产物β-紫罗兰酮的产量为0.87mg/L。本研究证明了[具体红酵母名称]作为各种萜类化合物直接生物合成的平台宿主的潜力,并为进一步开发此类平台提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/118f/11058065/4e3e98df740e/gr1.jpg

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