Multi-modular metabolic engineering of heme synthesis in Corynebacterium glutamicum  

作　　者：Qiuyu Yang Xi Sun Hong Wang Tao Chen Zhiwen Wang 

机构地区：[1]Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education),Tianjin University,Tianjin,300072,China [2]SynBio Research Platform,Collaborative Innovation Center of Chemical Science and Engineering(Tianjin),School of Chemical Engineering and Technology,Tianjin University,Tianjin,300072,China [3]School of Life Science,Ningxia University,Yinchuan,750021,China

出　　处：《Synthetic and Systems Biotechnology》2024年第2期285-293,共9页合成和系统生物技术（英文）

基　　金：This work was financially supported by the National Key Research and Development Program of China,China(2021YFC2100700);the National Natural Science Foundation of China,China(NSFC-22278312).

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.

关 键 词：Corynebacterium glutamicum HEME Biosynthetic pathways Metabolic engineering 

分 类 号：Q78[生物学—分子生物学]