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...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.展开更多
Methylotrophic yeasts and bacteria, which can use methanol as carbon and energy source, have beenwildly used as microbial cell factories for biomanufacturing. Due to their robustness in industrial harshconditions, met...Methylotrophic yeasts and bacteria, which can use methanol as carbon and energy source, have beenwildly used as microbial cell factories for biomanufacturing. Due to their robustness in industrial harshconditions, methylotrophic yeasts such as Pichia pastoris have been explored as a cell factory forproduction of proteins and high-value chemicals. Methanol utilization pathway （MUT） is highlyregulated for efficient methanol utilization, and the downstream pathways need extensively constructedand optimized toward target metabolite biosynthesis. Here, we present an overview of methanolmetabolism and regulation in methylotrophic yeasts, among which we focus on the regulation of keygenes involved in methanol metabolism. Besides, the recent progresses in construction and optimizationof downstream biosynthetic pathways for production of high value chemicals, such as polyketides, fattyacids and isoprenoids, are further summarized. Finally, we discuss the current challenges and feasiblestrategies toward constructing efficient methylotrophic cell factories may promote wide applications inthe future.展开更多
Coumarin and its derivatives,presenting in many organisms(plants,fungi,and bacteria),are critical metabolites composed of fused benzene andα-pyrone rings.With unique biological and chemical properties,coumarin deriva...Coumarin and its derivatives,presenting in many organisms(plants,fungi,and bacteria),are critical metabolites composed of fused benzene andα-pyrone rings.With unique biological and chemical properties,coumarin derivatives possess great technological potential in the agrochemicals,pharmaceuticals,food,and cosmetic industries.The increasing demand for coumarin derivatives accelerates the research in biological and chemical synthesis to provide stable and scalable sources of coumarins.However,the complex structures and unknown pathways have limited the progress in the biosynthesis of coumarin derivatives.Here,we summarize recent developments and provide a detailed analysis of coumarin derivative biosynthetic pathways in different organisms.展开更多
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).
文摘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.
基金funded by the Young Investigator Grant from Dalian Institute of Chemicals Physics,Chinese Academy of Sciences(to Y.J.Zhou)
文摘Methylotrophic yeasts and bacteria, which can use methanol as carbon and energy source, have beenwildly used as microbial cell factories for biomanufacturing. Due to their robustness in industrial harshconditions, methylotrophic yeasts such as Pichia pastoris have been explored as a cell factory forproduction of proteins and high-value chemicals. Methanol utilization pathway （MUT） is highlyregulated for efficient methanol utilization, and the downstream pathways need extensively constructedand optimized toward target metabolite biosynthesis. Here, we present an overview of methanolmetabolism and regulation in methylotrophic yeasts, among which we focus on the regulation of keygenes involved in methanol metabolism. Besides, the recent progresses in construction and optimizationof downstream biosynthetic pathways for production of high value chemicals, such as polyketides, fattyacids and isoprenoids, are further summarized. Finally, we discuss the current challenges and feasiblestrategies toward constructing efficient methylotrophic cell factories may promote wide applications inthe future.
基金supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM128620the support from the College of Engineering,The University of Georgia,Athens
文摘Coumarin and its derivatives,presenting in many organisms(plants,fungi,and bacteria),are critical metabolites composed of fused benzene andα-pyrone rings.With unique biological and chemical properties,coumarin derivatives possess great technological potential in the agrochemicals,pharmaceuticals,food,and cosmetic industries.The increasing demand for coumarin derivatives accelerates the research in biological and chemical synthesis to provide stable and scalable sources of coumarins.However,the complex structures and unknown pathways have limited the progress in the biosynthesis of coumarin derivatives.Here,we summarize recent developments and provide a detailed analysis of coumarin derivative biosynthetic pathways in different organisms.
