谷氨酸棒杆菌
血红素
卟啉
化学
合成生物学
代谢工程
生物化学
血红素A
发酵
蛋白质工程
组合化学
计算生物学
酶
生物
基因
作者
Qiuyu Yang,Xi Sun,Hong Wang,Tao Chen,Zhiwen Wang
标识
DOI:10.1016/j.synbio.2024.02.008
摘要
Heme, an iron-containing porphyrin derivative, holds great promise in fields like medicine, food production and chemicals. Here, we developed an engineered Corynebacterium glutamicum strain for efficient heme production by combining modular engineering and RBS engineering. The whole heme biosynthetic pathway was methodically divided into 5-ALA synthetic module, uroporphyrinogen III (UPG III) synthetic module and heme synthetic module for further construction and optimization. Three heme synthetic modules were compared and the siroheme-dependent (SHD) pathway was identified to be optimal in C. glutamicum for the first time. To further improve heme production, the expression of genes in UPG III synthetic module and heme synthetic module was coordinated optimized through RBS engineering, respectively. Subsequently, heme oxygenase was knocked out to reduce heme degradation. The engineered strain HS12 showed a maximum iron-containing porphyrin derivatives titer of 1592 mg/L with the extracellular secretion rate of 45.5% in fed-batch fermentation. Our study constructed a C. glutamicum chassis strain for efficient heme accumulation, which was beneficial for the advancement of efficient heme and other porphyrins production.
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