As advances in microbial engineering aim to meet goals in sustainable bioproduction, designer pharmaceuticals, and environmental monitoring, engineered functions are often hampered by poor host fitness. Growth defects incurred from high expression of heterologous proteins reduce host productivity and leave engineered populations vulnerable to displacement by nonfunctional mutants. Related, in contrived environments such as a bioreactor many expressed genes are detrimental to cellular fitness. We are developing proteomics-guided genome remodeling strategies to increase cellular capacity for heterologous expression. This work includes cellular capacity optimization in a massive genome reduction E. coli variant as well as cross-evaluation of bacteria adapted to human gut, marine marsh and plant rhizosphere environments. We expect this work to inform generalized genome remodeling strategies that eliminate the dispensable proteome while maintaining physiological robustness, leading to a better understanding of cellular responses to engineered loads and control of the longevity of engineered functions in complex microbial communities.

Data-driven cellular capacity optimization

256th National Meeting (2018)

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