Enhanced Production of High-Value Porphyrin Compound Heme by Metabolic Engineering Modification and Mixotrophic Cultivation of Synechocystis sp. PCC6803

被引:0
作者
Cao, Kai [1 ,2 ]
Sun, Fengjie [3 ]
Xin, Zechen [1 ]
Cao, Yujiao [2 ]
Zhu, Xiangyu [2 ]
Tian, Huan [1 ]
Cao, Tong [1 ]
Ma, Jinju [1 ]
Mu, Weidong [2 ]
Sun, Jiankun [1 ]
Zhou, Runlong [1 ]
Gao, Zhengquan [1 ]
Meng, Chunxiao [1 ]
机构
[1] Binzhou Med Univ, Sch Pharm, Yantai 264003, Peoples R China
[2] Shandong Univ Technol, Sch Life Sci & Med, Zibo 255049, Peoples R China
[3] Georgia Gwinnett Coll, Sch Sci & Technol, Dept Biol Sci, Lawrenceville, GA 30043 USA
基金
中国国家自然科学基金;
关键词
heme; Synechocystis sp. PCC6803; cell factory; metabolic transformation; ESCHERICHIA-COLI; PATHWAY; BIOSYNTHESIS; PHYCOCYANIN; MICROALGAE; EXPRESSION; ACETONE;
D O I
10.3390/md22090378
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Heme, as an essential cofactor and source of iron for cells, holds great promise in various areas, e.g., food and medicine. In this study, the model cyanobacteria Synechocystis sp. PCC6803 was used as a host for heme synthesis. The heme synthesis pathway and its competitive pathway were modified to obtain an engineered cyanobacteria with high heme production, and the total heme production of Synechocystis sp. PCC6803 was further enhanced by the optimization of the culture conditions and the enhancement of mixotrophic ability. The co-expression of hemC, hemF, hemH, and the knockout of pcyA, a key gene in the heme catabolic pathway, resulted in a 3.83-fold increase in the heme production of the wild type, while the knockout of chlH, a gene encoding a Mg-chelatase subunit and the key enzyme of the chlorophyll synthesis pathway, resulted in a 7.96-fold increase in the heme production of the wild type; further increased to 2.05 mg/L, its heme production was 10.25-fold that of the wild type under optimized mixotrophic culture conditions. Synechocystis sp. PCC6803 has shown great potential as a cell factory for photosynthetic carbon sequestration for heme production. This study provides novel engineering targets and research directions for constructing microbial cell factories for efficient heme production.
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页数:21
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