Nowadays,biological databases are playing an increasingly critical role in biological research.Myceliophthora thermophila is an excellent thermophilic fungal chassis for industrial enzyme production and plant biomass-...Nowadays,biological databases are playing an increasingly critical role in biological research.Myceliophthora thermophila is an excellent thermophilic fungal chassis for industrial enzyme production and plant biomass-based chemical synthesis.The lack of a dedicated public database has made access to and reanalysis of M.thermophila data difficult.To bridge this gap,we developed MTD(https://mtd.biodesign.ac.cn/),a cloud-based omics database and interactive platform for M.thermophila.MTD integrates comprehensive genome annotations,sequence-based predictions,transcriptome data,curated experimental descriptions,and bioinformatics analysis tools,offering a comprehensive,one-stop solution with a‘top-down’search strategy to streamline M.thermophila research.The platform supports data reproduction,rapid querying,and in-depth mining of existing tran-scriptome datasets.Based on analyses using data and tools in MTD,we identified shifts in metabolic allocation in a glucoamylase hyperproduction strain of M.thermophila,highlighting changes in fatty acid biosynthesis and amino acids biosynthesis pathways,which provide new insights into the underlying phenotypic alterations.As a pioneering resource,MTD marks a key advancement in M.thermophila research and sets the model for developing similar databases for other species.展开更多
High-quality genome-scale metabolic models(GEMs)could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology studies.Despite of the const...High-quality genome-scale metabolic models(GEMs)could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology studies.Despite of the constant establishment and update of GEMs for model microorganisms such as Escherichia coli and Saccharomyces cerevisiae,high-quality GEMs for non-model industrial microorganisms are still scarce.Zymomonas mobilis subsp.mobilis ZM4 is a non-model ethanologenic microorganism with many excellent industrial characteristics that has been developing as microbial cell factories for biochemical production.Although five GEMs of Z.mobilis have been constructed,these models are either generating ATP incorrectly,or lacking information of plasmid genes,or not providing standard format file.In this study,a high-quality GEM iZM516 of Z.mobilis ZM4 was constructed.The information from the improved genome annotation,literature,datasets of Biolog Phenotype Microarray studies,and recently updated Gene-Protein-Reaction information was combined for the curation of iZM516.Finally,516 genes,1389 reactions,1437 metabolites,and 3 cell compartments are included in iZM516,which also had the highest MEMOTE score of 91%among all published GEMs of Z.mobilis.Cell growth was then predicted by iZM516,which had 79.4%agreement with the experimental results of the substrate utilization.In addition,the potential endogenous succinate synthesis pathway of Z.mobilis ZM4 was proposed through simulation and analysis using iZM516.Furthermore,metabolic engineering strategies to produce succinate and 1,4-butanediol(1,4-BDO)were designed and then simulated under anaerobic condition using iZM516.The results indicated that 1.68 mol/mol succinate and 1.07 mol/mol 1,4-BDO can be achieved through combinational metabolic engineering strategies,which was comparable to that of the model species E.coli.Our study thus not only established a high-quality GEM iZM516 to help understand and design microbial cell factories for economic biochemical production using Z.mobilis as the chassis,but also provided guidance on building accurate GEMs for other non-model industrial microorganisms.展开更多
基金funded by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDC0110300)the National Key R&D Program of China(2023YFC3403602 and 2022YFC2106000)+2 种基金National Natural Science Foundation of China(32300529,32270100,and 32271481)the Innovation Fund of Haihe Laboratory of Synthetic Biology(22HHSWSS00014)the Tianjin Synthetic Biotechnology Inno-vation Capacity Improvement Project(TSBICIP-PTJJ-007-12).
文摘Nowadays,biological databases are playing an increasingly critical role in biological research.Myceliophthora thermophila is an excellent thermophilic fungal chassis for industrial enzyme production and plant biomass-based chemical synthesis.The lack of a dedicated public database has made access to and reanalysis of M.thermophila data difficult.To bridge this gap,we developed MTD(https://mtd.biodesign.ac.cn/),a cloud-based omics database and interactive platform for M.thermophila.MTD integrates comprehensive genome annotations,sequence-based predictions,transcriptome data,curated experimental descriptions,and bioinformatics analysis tools,offering a comprehensive,one-stop solution with a‘top-down’search strategy to streamline M.thermophila research.The platform supports data reproduction,rapid querying,and in-depth mining of existing tran-scriptome datasets.Based on analyses using data and tools in MTD,we identified shifts in metabolic allocation in a glucoamylase hyperproduction strain of M.thermophila,highlighting changes in fatty acid biosynthesis and amino acids biosynthesis pathways,which provide new insights into the underlying phenotypic alterations.As a pioneering resource,MTD marks a key advancement in M.thermophila research and sets the model for developing similar databases for other species.
基金the National Key Technology Research and Development Program of China(2018YFA0900300 and 2022YFA0911800)the National Natural Science Foundation of China(21978071 and U1932141)+3 种基金the Key Science and Technology Innovation Project of Hubei Province(2021BAD001)2022 Joint Projects between Chinese and CEEC’s Universities(202004)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Province(2018R01014)the Innovation Base for Introducing Talents of Discipline of Hubei Province(2019BJH021)。
文摘High-quality genome-scale metabolic models(GEMs)could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology studies.Despite of the constant establishment and update of GEMs for model microorganisms such as Escherichia coli and Saccharomyces cerevisiae,high-quality GEMs for non-model industrial microorganisms are still scarce.Zymomonas mobilis subsp.mobilis ZM4 is a non-model ethanologenic microorganism with many excellent industrial characteristics that has been developing as microbial cell factories for biochemical production.Although five GEMs of Z.mobilis have been constructed,these models are either generating ATP incorrectly,or lacking information of plasmid genes,or not providing standard format file.In this study,a high-quality GEM iZM516 of Z.mobilis ZM4 was constructed.The information from the improved genome annotation,literature,datasets of Biolog Phenotype Microarray studies,and recently updated Gene-Protein-Reaction information was combined for the curation of iZM516.Finally,516 genes,1389 reactions,1437 metabolites,and 3 cell compartments are included in iZM516,which also had the highest MEMOTE score of 91%among all published GEMs of Z.mobilis.Cell growth was then predicted by iZM516,which had 79.4%agreement with the experimental results of the substrate utilization.In addition,the potential endogenous succinate synthesis pathway of Z.mobilis ZM4 was proposed through simulation and analysis using iZM516.Furthermore,metabolic engineering strategies to produce succinate and 1,4-butanediol(1,4-BDO)were designed and then simulated under anaerobic condition using iZM516.The results indicated that 1.68 mol/mol succinate and 1.07 mol/mol 1,4-BDO can be achieved through combinational metabolic engineering strategies,which was comparable to that of the model species E.coli.Our study thus not only established a high-quality GEM iZM516 to help understand and design microbial cell factories for economic biochemical production using Z.mobilis as the chassis,but also provided guidance on building accurate GEMs for other non-model industrial microorganisms.
