Industrial Metabolic Engineering

工业代谢工程

• 批准号: 7219085
• 负责人: J. Mark Weber
• 金额: $ 21.06万
• 依托单位: FERMALOGIC, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2008-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7219085
• 关键词: Actinobacteria class; Actinomyces; Affect; Agriculture; Animal Model; Antibiotics; Antineoplastic Agents; Bacteria; Biochemical Genetics; Biological; Biological Assay; Biological Factors; Businesses; Cells; Chemicals; China; Classification; Condition; Croatia; Development; Engineering; Erythromycin; Escherichia coli; Feasibility Studies; Fermentation; Figs - dietary; Foundations; Generations; Genetic; Genetic Engineering; Genetic Models; Genome; Goals; Immunosuppressive Agents; In Vitro; India; Knowledge; Laboratories; Lead; Libraries; Manufacturer Name; Marketing; Medical; Metabolic; Metabolism; Methods; Methylmalonyl-CoA Mutase; Mexico; Mutagenesis; Mutate; Mutation; Names; Numbers; Organism; Pharmaceutical Preparations; Phase; Plasmids; Process; Production; Purpose; Range; Reaction; Research; Scientist; Screening procedure; Soil; Solid; Technology; Testing; Today; United States National Institutes of Health; base; commercial application; commercialization; design; drug testing; improved; interest; microorganism; miniaturize; multidisciplinary; mutant; programs; technological innovation

DESCRIPTION (provided by applicant): A type of metabolic engineering described in this proposal, and referred to as "industrial" metabolic engineering, is a method for performing strain improvement in industrial microorganisms by harnessing the power of in vitro transposition mutagenesis. The industrial microorganisms of interest to this study are the actinomycetes, a group of soil bacteria that are best known for their ability to produce over two thirds of the worlds naturally derived antibiotics, anticancer agents, and immunosuppressants currently in medical use. Industrial metabolic engineering also benefits from technical progress made in microfermentation screening. Microfermentations make possible the economical screening of large numbers of mutants in order find improved strains. Because of the transposon tagging process, these improved mutants can be easily reverse engineered to reveal the identity of the strain improvement mutation they harbor in their genome. Once the strain improvement target is identified, new genetic and metabolic knowledge is revealed that can lead to further optimization of the technology and extension of the technology to other industrial fermentation processes of medical importance. The model organism used in this study is the erythromycin producing organism, S. erythraea, that has been the subject of over 50 years of intensive genetic and biochemical research, providing a solid foundation upon which to build the fundamentals for the emerging field of predictive metabolic engineering of industrial microorganisms. 1 PROJECTNARRATIVE Industrial Metabolic Engineering Metabolic engineering will someday give scientists the ability to predicatively manipulate biological organisms for many useful purposes ranging from strain improvement and other industrial biotech applications, to allowing greater agricultural production, permitting more efficient and safer energy production, and providing better understanding of the metabolic basis for medical conditions that will assist in the development of new cures. For some promising new natural products, our technology could make the difference between a drug making it to market, or being abandoned due to inadequate supply of the drug for testing or commercial distribution.

描述（由申请人提供）：本提案中描述的一种代谢工程，被称为“工业”代谢工程，是一种通过利用体外替代型诱变的力量来改善工业微生物的应变方法。这项研究感兴趣的工业微生物是放线菌，这是一组土壤细菌，它们以其生产自然衍生的抗生素，抗癌剂和免疫抑制剂目前目前在医用医学用途中生产三分之二的世界的能力而闻名。工业代谢工程也受益于微观筛查中的技术进度。小额审查使得对大量突变体的经济筛查有可能找到改善的菌株。由于转座标记过程，这些改进的突变体可以很容易地进行逆转，以揭示其在基因组中携带的菌株改善突变的身份。一旦确定了菌株改善目标，就会发现新的遗传和代谢知识可以进一步优化技术，并将技术扩展到其他医学重要性的其他工业发酵过程。这项研究中使用的模型有机体是产生红霉素的红细胞链球菌，它是超过50年的密集遗传和生化研究的主题，为工业微观机构的预测代谢工程的新兴代谢工程的新兴领域提供了扎实的基础。 1项目纳尔工业代谢工程代谢工程将使科学家能够为许多有用的目的而主张操纵生物有机体，从应变改善和其他工业生物技术应用，到使更高的农业生产，使能源生产更有效，更安全地生产能够更好地了解新的疾病，从而有助于使用新的状况。对于一些有前途的新天然产品，我们的技术可能会使该药物进入市场，或者由于无法进行测试或商业分销的药物而被放弃。

项目成果

Random transposon mutagenesis of the Saccharopolyspora erythraea genome reveals additional genes influencing erythromycin biosynthesis.

• DOI: 10.1093/femsle/fnv180
• 发表时间: 2015-11
• 期刊: FEMS microbiology letters
• 影响因子: 2.1
• 作者: Andrij Fedashchin;William H. Cernota;Melissa C. Gonzalez;Benjamin I. Leach;Noelle Kwan;R. Wesley;J. Weber