期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 70, 期 8, 页码 2673-2683出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c08072
关键词
astaxanthin; yarrowia lipolytica; beta-carotene hydroxylase; beta-carotene ketolase
资金
- Chinese Academy of Agricultural Sciences [Y2020XK25, CAAS-XTCX2018020-7]
This study successfully engineered Yarrowia lipolytica to produce high levels of 3S,3'S-astaxanthin, providing potential for industrial production and laying the foundation for a sustainable biorefinery platform.
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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