Production of High Levels of 3S,3 ' S-Astaxanthin in Yarrowia lipolytica via Iterative Metabolic Engineering

文献类型： 外文期刊

第一作者： Zhu, Hang-Zhi

作者： Zhu, Hang-Zhi;Jiang, Shan;Wu, Jun-Jie;Liu, Peng-Yang;Huang, Feng-Hong;Wan, Xia;Zhou, Xue-Rong;Huang, Feng-Hong;Wan, Xia;Huang, Feng-Hong;Wan, Xia

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关键词： astaxanthin; yarrowia lipolytica; beta-carotene hydroxylase; beta-carotene ketolase

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.895； 五年影响因子：6.048 ）

ISSN： 0021-8561

年卷期： 2022 年 70 卷 8 期

页码：

收录情况： SCI

摘要： Astaxanthin is a highly value-added keto-carotenoid compound. The astaxanthin 3S,3'S-isomer is more desirable for food additives, cosmetics, and pharmaceuticals due to health concerns about chemically synthesized counterparts with a mixture of three isomers. Biosynthesis of 3S,3'S-astaxanthin suffers from limited content and productivity. We engineered Yarrowia lipolytica to produce high levels of 3S,3'S-astaxanthin. We first assessed various beta-carotene ketolases (CrtW) and beta-carotene hydroxylases (CrtZ) from two algae and a plant. HpCrtW and HpCrtZ from Haematococcus pluvialis exhibited the strongest activity in converting beta-carotene into astaxanthin in Y. lipolytica. We then fine-tuned the HpCrtW and HpCrtZ transcriptional expression by increasing the rounds of gene integration into the genome and applied a modular enzyme assembly of HpCrtW and HpCrtZ simultaneously. Next, we rescued leucine biosynthesis in the engineered Y. lipolytica, leading to a five-fold increase in biomass. The astaxanthin production achieved from these strategies was 3.3 g/L or 41.3 mg/g dry cell weight under fed-batch conditions, which is the highest level reported in microbial chassis to date. This study provides the potential for industrial production of 3S,3'S-astaxanthin, and this strategy empowers us to build a sustainable biorefinery platform for generating other value-added carotenoids in the future.

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