Synthetic control of a fitness tradeoff in yeast nitrogen metabolism.
Synthetic control of a fitness tradeoff in yeast nitrogen metabolism.
复制标题
DOI：
10.1186/1754-1611-3-1
复制
发表时间：
2009-01-02
影响因子：
5.6
通讯作者：
Smolke CD
中科院分区：
文献类型：
--
作者：
Bayer TS;Hoff KG;Beisel CL;Lee JJ;Smolke CD
微生物群落参与与工业和医学生物技术相关的许多过程，例如生物膜的形成、木质纤维素降解和氢气生产。合成和天然微生物群落及其潜在生态参数（例如适应性、进化性和变异性）的操纵是合成生物学日益重要的研究领域。在这里，我们探索了如何使用内源回路的综合控制来调节酿酒酵母种群中资源丰富和资源有限环境的适应性之间的权衡。我们发现氨同化中关键酶 Gdh1p 表达中的噪音介导了低氮环境中的生长和高氨环境中的抗逆性之间的权衡。我们对内源性 Gdh1p 调控网络进行了综合控制，以构建一种工程菌株，其中群体的适应性可以在一系列氨环境中响应外源添加的小分子而进行调节。调整适应性和生物权衡的能力将是未来设计微生物群落的重要组成部分。
Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities.