Methylotrophic yeast has been used as a cost-effective and valuable host for expression of recombinant protein due to its unique methanol utilisation pathway. It has an AOX （alcohol oxidase） protein which has been c...Methylotrophic yeast has been used as a cost-effective and valuable host for expression of recombinant protein due to its unique methanol utilisation pathway. It has an AOX （alcohol oxidase） protein which has been characterised to be a strong and tightly methanol-inducible dependent promoter. Metabolomics is the systematic study and inclusive analysis of small molecules called metabolites in a biological system. Metabolomics plays an important part in connecting the phenotype and genotype gap because it magnifies the modifications in the proteome and provides a better phenotype representation of an organism. This quantitative study has provided a new perception on the metabolic burden derived from the overexpression of recombinant protein in methylotrophic yeast. In this review, we discuss the fundamental aspect of metabolomics in methylotrophic yeast followed by their latest developments.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
Methanol is an attractive C1 feedstock with high abundance and low cost in bio-manufacturing.However,the metabolic construction of cell factories to utilize methanol for chemicals production remains a challenge due to...Methanol is an attractive C1 feedstock with high abundance and low cost in bio-manufacturing.However,the metabolic construction of cell factories to utilize methanol for chemicals production remains a challenge due to the toxic intermediates and complicated metabolic pathways.The group of Zhou rescued methylotrophic yeast from cell death and achieved high-level production of free fatty acids from methanol through a combination of adaptive laboratory evolution,rational metabolic engineering and multi-omics analysis.展开更多
文摘Methylotrophic yeast has been used as a cost-effective and valuable host for expression of recombinant protein due to its unique methanol utilisation pathway. It has an AOX （alcohol oxidase） protein which has been characterised to be a strong and tightly methanol-inducible dependent promoter. Metabolomics is the systematic study and inclusive analysis of small molecules called metabolites in a biological system. Metabolomics plays an important part in connecting the phenotype and genotype gap because it magnifies the modifications in the proteome and provides a better phenotype representation of an organism. This quantitative study has provided a new perception on the metabolic burden derived from the overexpression of recombinant protein in methylotrophic yeast. In this review, we discuss the fundamental aspect of metabolomics in methylotrophic yeast followed by their latest developments.
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This work was supported by National Key R&D Program of China(2018YFA0901500)the National Natural Science Foundation of China(22078151,21978130)+1 种基金Young Elite Scientist Sponsorship Program by CAST(YESS20200174)Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture.
文摘Methanol is an attractive C1 feedstock with high abundance and low cost in bio-manufacturing.However,the metabolic construction of cell factories to utilize methanol for chemicals production remains a challenge due to the toxic intermediates and complicated metabolic pathways.The group of Zhou rescued methylotrophic yeast from cell death and achieved high-level production of free fatty acids from methanol through a combination of adaptive laboratory evolution,rational metabolic engineering and multi-omics analysis.
