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Complete pathway elucidation and heterologous reconstitution of (+)-nootkatone biosynthesis from Alpinia oxyphylla

文献类型： 外文期刊

作者： Deng, Xiaomin 1 ; Ye, Ziling 4 ; Duan, Jingyu 3 ; Chen, Fangfang 3 ; Zhi, Yao 3 ; Huang, Man 4 ; Huang, Minjian 3 ; Cheng, Weijia 3 ; Dou, Yujie 3 ; Kuang, Zhaolin 3 ; Huang, Yanglei 3 ; Bian, Guangkai 3 ; Deng, Zixin 3 ; Liu, Tiangang 2 ; Lu, Li 2 ;

作者机构： 1.Chinese Acad Trop Agr Sci, Rubber Res Inst, Natl Key Lab Trop Crop Breeding,State Key Lab Bree, Minist Agr Key Lab Biol & Genet Resources Rubber T, Haikou 571101, Hainan, Peoples R China

2.Wuhan Univ, Zhongnan Hosp, Sch Pharmaceut Sci, Dept Urol, Wuhan 430071, Peoples R China

3.Wuhan Univ, Sch Pharmaceut Sci, Key Lab Combinatorial Biosynth & Drug Discovery, Minist Educ, Wuhan 430071, Hubei, Peoples R China

4.Wuhan Hesheng Technol Co Ltd, Wuhan 430074, Hubei, Peoples R China

5.Wuhan Univ, Taikang Med Sch, Wuhan 430071, Hubei, Peoples R China

6.Hubei Hongshan Lab, Wuhan 430071, Hubei, Peoples R China

关键词： Alpinia oxyphylla; (+)-nootkatone; plant specialised metabolic pathway; Saccharomyces cerevisiae; sesquiterpenoid biosynthesis; (+)-valencene

期刊名称：NEW PHYTOLOGIST （ 影响因子：9.4； 五年影响因子：10.5 ）

ISSN： 0028-646X

年卷期： 2023 年

页码：

收录情况： SCI

摘要： (+)-Nootkatone is a natural sesquiterpene ketone widely used in food, cosmetics, pharmaceuticals, and agriculture. It is also regarded as one of the most valuable terpenes used commercially. However, plants contain trace amounts of (+)-nootkatone, and extraction from plants is insufficient to meet market demand. Alpinia oxyphylla is a well-known medicinal plant in China, and (+)-nootkatone is one of the main components within the fruits.By transcriptome mining and functional screening using a precursor-providing yeast chassis, the complete (+)-nootkatone biosynthetic pathway in Alpinia oxyphylla was identified.A (+)-valencene synthase (AoVS) was identified as a novel monocot-derived valencene synthase; three (+)-valencene oxidases AoCYP6 (CYP71BB2), AoCYP9 (CYP71CX8), and AoCYP18 (CYP701A170) were identified by constructing a valencene-providing yeast strain. With further characterisation of a cytochrome P450 reductase (AoCPR1) and three dehydrogenases (AoSDR1/2/3), we successfully reconstructed the (+)-nootkatone biosynthetic pathway in Saccharomyces cerevisiae, representing a basis for its biotechnological production.Identifying the biosynthetic pathway of (+)-nootkatone in A. oxyphylla unravelled the molecular mechanism underlying its formation in planta and also supported the bioengineering production of (+)-nootkatone. The highly efficient yeast chassis screening method could be used to elucidate the complete biosynthetic pathway of other valuable plant natural products in future.

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