Development of a green Komagataella phaffii cell factory for sustainable production of plant-derived sesquiterpene (–)-α-bisabolol

IF 4.4 2区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jintao Cheng , Zhongji Pu , Jiali Chen , Dingfeng Chen , Baoxian Li , Zhengshun Wen , Yuanxiang Jin , Yanlai Yao , Kan Shao , Xiaosong Gu , Guiling Yang
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Abstract

(–)-α-Bisabolol is a plant-derived sesquiterpene derived from Eremanthus erythropappus, which can be used as a raw material in cosmetics and has anti-inflammatory function. In this study, we designed six mutation sites of the (–)-α-bisabolol synthase BOS using the plmDCA algorithm. Among these, the F324Y mutation demonstrated exceptional performance, increasing the product yield by 73 %. We constructed a de novo (–)-α-bisabolol biosynthesis pathways through systematic synthetic biology strategies, including the enzyme design of BOS, selection of different linkers in fusion expression, and optimization of the mevalonate pathway, weakening the branching metabolic flow and multi-copy strategies, the yield of (–)-α-bisabolol was significantly increased, which was nearly 35-fold higher than that of the original strain (2.03 mg/L). The engineered strain was capable of producing 69.7 mg/L in shake flasks. To the best of our knowledge, this is the first report on the biosynthesis of (–)-α-bisabolol in Komagataella phaffii, implying this is a robust cell factory for sustainable production of other terpenoids.

Abstract Image

开发绿色 Komagataella phaffii 细胞工厂,以可持续方式生产植物源倍半萜 (-)-α-bisabolol
(-)-α-双羟基苯甲酸酯是一种植物源倍半萜,来自红花楹,可用作化妆品原料,具有抗炎作用。在这项研究中,我们利用 plmDCA 算法设计了 (-)-α-bisabol 合成酶 BOS 的六个突变位点。其中,F324Y 突变位点表现出优异的性能,使产物产量提高了 73%。我们通过系统的合成生物学策略,包括BOS的酶设计、融合表达中不同连接子的选择、甲羟戊酸途径的优化、弱化分支代谢流和多拷贝策略,构建了一条全新的(-)-α-二羟基苯并酚生物合成途径,(-)-α-二羟基苯并酚的产率显著提高,比原始菌株(2.03 mg/L)提高了近35倍。工程菌株在摇瓶中的产量为 69.7 毫克/升。据我们所知,这是首次报道 Komagataella phaffii 中 (-)-α-bisabol 的生物合成,这意味着这是一个可持续生产其他萜类化合物的强大细胞工厂。
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来源期刊
Synthetic and Systems Biotechnology
Synthetic and Systems Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
6.90
自引率
12.50%
发文量
90
审稿时长
67 days
期刊介绍: Synthetic and Systems Biotechnology aims to promote the communication of original research in synthetic and systems biology, with strong emphasis on applications towards biotechnology. This journal is a quarterly peer-reviewed journal led by Editor-in-Chief Lixin Zhang. The journal publishes high-quality research; focusing on integrative approaches to enable the understanding and design of biological systems, and research to develop the application of systems and synthetic biology to natural systems. This journal will publish Articles, Short notes, Methods, Mini Reviews, Commentary and Conference reviews.
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