Optimizing metabolic functions in microbial production using synchronized populations

现在，使用微生物过程来生产分子的方式和数量是可能的，直到最近，人们还认为这是不可能的。不断开发和改进新的战略，以在能源、制药和生物材料等各种领域创造增值产品。虽然这些进展中的许多在实验室是有希望的，但将它们转化为经济上可行的过程往往是一个挑战。因此，将基因工具和生物过程的开发结合起来越来越重要。限制生物生产优化的另一个重要因素是一个群体中的细胞表现出各种各样的不同行为。**我最近的一些工作表明，使用自循环培养同步的大肠杆菌种群-一种获得年龄分布较窄的细胞种群的非侵入性、基于过程的方法-显示出生长相关产品(噬菌体和重组蛋白)的生产率提高。因此，同步过程可能导致有益的新陈代谢功能的重新分配。**拟议的研究计划旨在确定影响同步大肠杆菌种群生产力提高的代谢因素。根据这些结果，将努力开发基因工具和生物处理策略，以提高具有同步微生物种群的工程途径的生产率。这样，就有可能把整个微生物种群当作一个单一细胞来对待。这将允许在广泛的行业中对过程进行更严格的控制，并提高生物产品的产量。**该计划的另一个目标是培养过程工程、微生物学、分子生物学和代谢工程相结合的跨学科领域的学生。

It is now possible to use microbial processes to produce molecules in ways and quantities that were, until recently thought to be impossible. Novel strategies are constantly developed and improved to create value-added products in fields as varied as energy, pharmaceuticals and biomaterials. While many of these advances are promising in the laboratory, it is often a challenge to transfer them into economically viable processes. It is thus increasingly relevant to integrate the development of genetic tools and bioprocesses. Another important factor limiting the optimization of bio-production is the fact that cells in a population display a wide variety of different behaviors. ** Some of my recent work has shown that E. coli populations synchronized using self-cycling cultivation - a non-intrusive, process-based approach to obtaining cell populations with a narrow age distribution - displayed increased productivity of growth-associated products (phages and recombinant proteins). The synchronization process could thus lead to a beneficial reassignment of metabolic functions.**The proposed research program aims to identify the metabolic factors affecting this increase in productivity in synchronized E. coli populations. From these results, efforts will be made to develop genetic tools and bioprocessing strategies to improve productivity in engineered pathways with synchronized microbial populations. It will thus be possible to treat whole microbial populations as if it were a single cell. This will allow tighter control of processes and higher yields of bio-products in a wide array of industries. **Another objective of the program will be to train students in an interdisciplinary field combining process engineering, microbiology, molecular biology and metabolic engineering.**********