Optimizing metabolic functions in microbial production using synchronized populations

现在有可能利用微生物过程生产分子，其方式和数量直到最近才被认为是不可能的。在能源、制药和生物材料等领域，不断开发和改进新的战略，以创造增值产品。虽然许多这些进展在实验室中很有希望，但将它们转化为经济上可行的工艺往往是一个挑战。因此，整合遗传工具和生物过程的发展日益重要。限制生物生产优化的另一个重要因素是群体中的细胞表现出各种不同的行为。**我最近的一些工作表明，使用自循环培养（一种非侵入性的、基于过程的方法，以获得具有狭窄年龄分布的细胞群体）同步的大肠杆菌群体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代谢功能重新分配。**拟议的研究计划旨在确定影响同步大肠杆菌群体生产率提高的代谢因素。根据这些结果，将努力开发遗传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力。这样就有可能像对待单个细胞一样对待整个微生物种群。这将允许更严格的过程控制和更高的产量的生物产品在广泛的行业。**该计划的另一个目标将是培养学生在跨学科领域结合过程工程，微生物学，分子生物学和代谢工程。**********

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.**********