School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China.
Mar Drugs. 2024 Aug 23;22(9):378. doi: 10.3390/md22090378.
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 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 sp. PCC6803 was further enhanced by the optimization of the culture conditions and the enhancement of mixotrophic ability. The co-expression of , , , and the knockout of , 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 , 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. 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.
血红素作为细胞的必需辅因子和铁源，在食品和医药等领域具有广阔的应用前景。本研究以模式蓝藻 sp. PCC6803 为宿主进行血红素合成。通过对血红素合成途径及其竞争途径进行修饰，获得了一株具有高血红素产量的工程化蓝藻，并通过优化培养条件和增强混养能力进一步提高了 sp. PCC6803 的总血红素产量。共表达 、 、 ，以及敲除血红素降解途径中的关键基因 ，使野生型的血红素产量增加了 3.83 倍，而敲除编码 Mg-螯合酶亚基和叶绿素合成途径关键酶的基因 ，使野生型的血红素产量增加了 7.96 倍；进一步增加到 2.05mg/L，其血红素产量在优化的混养培养条件下是野生型的 10.25 倍。 sp. PCC6803 作为一种用于光合碳固存生产血红素的细胞工厂具有巨大的潜力。本研究为构建高效生产血红素的微生物细胞工厂提供了新的工程靶点和研究方向。
