Industrial Metabolic Engineering

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转位诱变的力量对工业微生物进行菌株改良的方法。本研究感兴趣的工业微生物是放线菌，放线菌是一组土壤细菌，以其生产目前世界上三分之二以上的天然抗生素、抗癌剂和免疫抑制剂的能力而闻名。工业代谢工程也受益于微发酵筛选技术的进步。微发酵使大量突变体的经济筛选成为可能，以便找到改良菌株。由于转座子标记过程，这些改进的突变体可以很容易地进行反向工程，以揭示它们在基因组中所携带的菌株改进突变的身份。一旦确定了菌株改良目标，就会揭示新的遗传和代谢知识，从而可以进一步优化技术并将该技术推广到其他具有医疗重要性的工业发酵过程中。本研究中使用的模式生物是红霉素产生生物S. erythraea，它是50多年来密集的遗传和生化研究的主题，为工业微生物预测代谢工程这一新兴领域提供了坚实的基础。工业代谢工程有一天，代谢工程将使科学家能够预测操纵生物有机体，用于许多有用的目的，从菌株改良和其他工业生物技术应用，到允许更大的农业生产，允许更有效和更安全的能源生产，并提供更好的理解代谢基础的医疗条件，这将有助于开发新的治疗方法。对于一些有前途的新天然产品，我们的技术可以使药物进入市场，或者由于药物供应不足而被放弃用于测试或商业分销。

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.