COLLABORATIVE RESEARCH: Exploiting microbial hyperthermophilicity to produce an industrial chemical

合作研究：利用微生物的超嗜热性来生产工业化学品

• 批准号: 1264053
• 负责人: Michael Adams
• 金额: $ 25.06万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1264053&HistoricalAwards=false
• 关键词: COLLABORATIVE; RESEARCH; Exploiting; microbial; hyperthermophilicity

1264052/1264053 Kelly/AdamsThe development of microbial metabolic engineering has largely been based on a limited number of recombinant hosts (e.g., Escherichia coli, Saccharomyces cerevisiae) because of the substantial knowledge of the physiology of these microorganisms and availabilityof associated molecular genetic tools. However, as metabolic engineering is directed at more and more innovative bioprocessing objectives, there is a pressing need to expand the range of potential microbial hosts. Because extremophiles are already endowed with properties that are amenable to the harsh conditions characteristic of industrial processes, it makes sense to develop metabolic engineering capabilities for this group of microorganisms. This direction would have been implausible until very recently, but newly developed molecular genetic tools and genomics studies have opened up the prospects for metabolic engineering of extremophiles. As such, this proposed project will demonstrate the efficacy of metabolically engineering the hyperthermophilic archaeon, Pyrococcus furiosus, which grows optimally at 100°C. To demonstrate that this microorganism can, indeed, be metabolically engineered, the work will build upon recent success in temperature-dependent biochemical processing and will now produce a specialty chemical, succinate, from cellobiose and maltose. Genes encoding transporters and metabolic enzymes identified from less thermophilic organisms with optimum temperature values near 70°C will be imported into a recombinant P. furiosus strain. Novel approaches for gene regulation and product formation that strategically exploit hyperthermophilicity will be utilized to optimize yields and efficiencies for bioproduct formation near 70°C. Providing a paradigm for metabolically engineering a hyperthermophilic host to produce a non-physiological product will pave the way for thermally-based, bioprocessing opportunities.Broader impacts will result from the interdisciplinary training of students in molecular biochemistry, functional genomics and biomolecular engineering for studying extremophile biology and biotechnology. Two undergraduate researchers will be recruited during each fall semester and be supported subsequently for a summer research experience in the PI's laboratories (one biochemist at UGA and one chemical engineer at NCSU). These students will spend two weeks during the summer at the other collaborating lab to foster interdisciplinary training. All students on this and related projects at NCSU and UGA will participate in an annual extended 'Hyperthermophile Group Meeting' during the summer to be hosted at NSCU and UGA on an alternating basis. This will foster interdisciplinary training and collegiality, as well as provide a mechanism for exchange of research ideas and methodologies.

1264052/1264053 Kelly/Adams的微生物代谢工程的发展主要基于有限数量的重组宿主（例如，大肠杆菌，大肠杆菌，酿酒酵母），因为对这些微生物的物理学的实质性了解和相关工具具有相关的概念工具，因此是因为具有实质性的知识。但是，由于代谢工程专门针对越来越创新的生物处理对象，因此需要扩大潜在微生物宿主的范围。由于极端友善已经具有适合工业过程的有害条件特征的特性，因此为这组微生物发展代谢工程能力是有意义的。直到最近，这个方向是令人难以置信的，但是新开发的分子遗传工具和基因组学研究为极端友善的代谢工程开辟了前景。因此，该提议的项目将证明代谢工程高疗法，即富洛群岛（Furococcus Furiosus）的有效性，该工具在100°C时最佳地生长。为了证明这种微生物的确可以代谢工程，这项工作将基于近期在温度依赖性生化加工方面的成功，现在将产生一种特殊的化学物质，即琥珀酸酯，来自核纤维和麦芽糖。编码从较少的嗜热生物鉴定出的具有优化温度值接近70°C的温度值的转运蛋白和代谢酶的基因将进口到重组菌菌菌株中。基因调节和产物形成的新方法，将利用高温性高的生物生物产物形成的产量和效率，以策略性地利用过度热素。为代谢工程提供范例，一种生产非生理学产品的宿主将为基于热的，生物处理机会铺平道路。Broader将由分子生物化学，功能性基因组学和生物分子工程学的分子生物化学和生物生物学工程学的研究生培训产生的影响。每个秋季学期将招募两名本科研究人员，并随后在PI实验室（UGA的一名生物化学家和NCSU的一名化学工程师）获得夏季研究经验。这些学生将在夏季在另一个合作实验室度过两个星期，以培养跨学科培训。 NCSU和UGA的所有与此有关的学生都将在夏季参加年度扩展的“热疗小组会议”，以其他方式在NSCU和UGA举办。这将培养跨学科的培训和合作，并为研究思想和方法交换提供机制。