CAREER: Unraveling the impact of decoupling the carbon metabolism of microbial cell factories on bioproduction

细胞生长和茁壮成长的需要通常限制了所需产物的产率和合成速率。细胞在这两种活动之间平衡能量和物质（通常是碳）的流动。这种限制是因为细胞倾向于一次使用单一的碳和能源。改变代谢，同时利用两种来源可以缓解这种限制。将每一种来源单独用于增长或产品形成可以消除目前的限制。应用计算方法将有助于实现这些修改。设计一个利用二氧化碳和糖以外的可再生原料的灵活生物精炼厂是我们的目标。该项目还将为代表性不足的本科生提供机会。 来自部落学校、纳瓦霍技术大学和Tohono O 'odham社区学院的学生将参与这一项目。参加Girls Make-A-通村将激励年轻女性在STEM领域学习。该项目的核心假设是，将碳代谢分解为多个隔间，其中每个隔间的碳通量来自不同的碳基质，将导致产品滴度，速率和产量增加。 将开发一个基于基因组规模建模的代谢解耦工具箱，以帮助识别代谢网络中的隔间。 上述假设将在两种情况下进行探讨。在一种情况下，两种碳底物将在蓝细菌Synechococcus sp. PCC 11901的单个细胞中转化为两种产物。 另一种情况将使用谷氨酸棒杆菌来稳定木质素，同时通过代谢葡萄糖来维持自身。此外，13 C途径分析将用于探索工程菌株的代谢，并进一步了解两种碳底物对生物生产的碳贡献。该奖项反映了NSF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。

The need for cells to grow and thrive often limits the yield and rate of synthesis of a desired product. The cell balances the flows of energy and material, usually carbon, between these two activities. This limitation arises because cells tend to use a single carbon and energy source at a time. Modifying metabolism to utilize two sources at the same time could alleviate the limitation. Directing each source solely to either growth or product formation could abolish the current limitations. Applying computational approaches will facilitate achievement of these modifications. Designing a flexible biorefinery utilizing renewable feedstocks other than carbon dioxide and sugars is the goal. The project will also provide opportunities for underrepresented undergraduate students. Students from tribal schools, Navajo Technical University and Tohono O'odham Community College, will be involved in this project. Participating in the Girls Make-A-Thon will inspire young women to study in STEM fields.The idea that decoupling carbon metabolism into compartments, wherein carbon flux through each compartment has its origin from a different carbon substrate, will lead to increased product titer, rate, and yield is the central hypothesis underlying this project. A metabolism decoupling toolbox based on genome scale modeling will be developed to aid in the identification of compartments within metabolic networks. The above hypothesis will be explored for two scenarios. In one case, two carbon substrates will be converted into two products in a single cell of the cyanobacterium Synechococcus sp. PCC 11901. The other case will use Corynebacterium glutamicum to valorize lignin while maintaining itself by metabolizing glucose. In addition, 13C-pathway analysis will be used to explore the metabolism of the engineered strains and to further understand the carbon contribution of the two carbon substrates towards bioproduction.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.