Industrial Metabolic Engineering

描述(申请人提供)：工业代谢工程是一种通过利用体外随机转座突变的力量在工业微生物中进行菌株改良的方法。我们在这项研究中旨在改进的生物是放线菌，这是一组土壤细菌，以其产生世界上三分之二以上的天然衍生抗生素、抗癌剂和目前用于医疗的免疫抑制剂的能力而闻名。转座子标记过程之所以强大，不仅是因为它能够使菌株发生改良突变，还因为它允许对菌株进行反向工程，以揭示受影响基因的身份。一旦确定了菌株改进的目标，新的遗传和代谢知识就会被揭示出来，这可能会导致该技术的进一步优化和推广到其他具有医学意义的生物上。这项研究中使用的模式生物是红霉素产生生物-红霉菌，这是一种经过50多年密集的遗传和生化研究的细菌，为工业微生物代谢工程这一新兴领域提供了坚实的基础。

DESCRIPTION (provided by applicant): Industrial metabolic engineering is a method for performing strain improvement in industrial microorganisms by harnessing the power of random in vitro transposition mutagenesis. The organisms we aim to improve in 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. The transposon tagging process is powerful not only because of its ability to make strain improvement mutations, but also because it allows strains to be easily reverse engineered to reveal the identity of the affected gene. Once the strain improvement target is identified, new genetic and metabolic knowledge is revealed that can lead to further optimization and extension of the technology to other organisms of medical importance. The model organism used in this study is the erythromycin producing organism, Saccharopolyspora erythraea, a bacterium 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 metabolic engineering of industrial microorganisms.