A foundational platform to engineer synthetic heterotrophy in yeast

贝克酵母是生产乙醇和复杂生物产品的重要生物，但它只能使用有限数量的碳源。各种可再生和/或廉价的碳源目前是可用的。扩大面包酵母利用这些来源生产生物产品的能力将是有益的。研究人员将试图发现控制酵母碳利用的机制。然后将制定设计原则，以帮助扩大可使用的碳源的范围。这将扩大可再生燃料和化学品的生产。研究生和本科生将参与本研究。他们还将参与社区外展工作，以提高工作对更大社区的可见度。非原生底物占可再生和廉价原料的很大一部分。很少有研究探索整合细胞调控对异源同化途径的益处。因此，这项工作的目标是1)证明细胞决策当用于将生长相关过程与非天然底物同化相结合时，对产生baker？S酵母可以在任何数量的结构多样化的底物上快速生长，2)这些见解可以用来开发一个通用的平台来设计和优化非天然底物的生长。这里开发的平台还将使功能基因组学研究能够以过去不可能的方式识别非天然底物代谢的调节剂。预计该项目的成果将超越作为该项目的重点的面包酵母和底物，因为这里开发的范式有望帮助其他工业相关微生物的类似努力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Baker's yeast is an important organism for producing ethanol and complex bioproducts, but it can use only a limited number of carbon sources. A variety of renewable and/or cheap carbon sources are currently available. Expanding the capacity of baker's yeast to use these sources to produce bioproducts would be beneficial. The investigators will attempt to discover the mechanisms that control carbon utilization in yeast. Design principles will then be developed to help expand the range of carbon sources that can be used. This will expand the production of renewable fuels and chemicals. Graduate and undergraduate students will participate in this research. They will also be engaged in community outreach efforts to enhance the visibility of the work to the larger community. Non-native substrates represent a significant fraction of renewable and inexpensive feedstocks. Little work has been done to explore the benefits of integrating cellular regulatory control over heterologous assimilation pathways. Therefore, goal of this work is to 1) demonstrate that cellular decision-making when used to couple growth-related processes with non-native substrate assimilation has significant benefits in generating strains of baker?s yeast that can rapidly grow on any number of structurally diverse substrates, and 2) that these insights can be leveraged to develop a universal platform to engineer and optimize growth on non-native substrates. The platform developed here will also enable functional genomics studies to identify modulators of non-native substrate metabolism in a manner not possible in the past. It is anticipated that the outcomes from the project will extend beyond baker's yeast and the substrates that are the focus of this project since the paradigm developed here is expected to aid similar efforts with other industrially relevant microbes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.