Novel Bioengineering Technique for Genome-Scale Tuning of Gene Expression


Introduction of new genes encoding desired functional attributes has long been a central tool for metabolic engineering and synthetic biodesign of microorganisms. However, difficulties in accurately predicting the expression levels of these genes in their new hosts significantly slow the design cycle and hinder progress. This is particularly problematic in synthetic biology, where large genetic constructs containing multiple genes are often introduced. Now researchers present a novel technique to more accurately predict gene expression levels in engineered biosystems by combining recent advances in DNA synthesis with novel, multiplexed methods for measuring DNA, RNA, and protein levels simultaneously using next-generation sequencing. This new technique allowed the team to simultaneously measure transcription and translation rates of thousands of synthetic regulatory elements introduced into the model microbe Escherichia coli . The resulting dataset was then used to model gene and protein expression levels under various sets of regulatory elements and “compose” a designed regulatory strategy that enables accurate prediction of expression levels of introduced genetic elements. This new technique has the potential to allow much more sophisticated forward design of genetic engineering strategies to improve production of biofuels and other bioproducts.


Kosuri, S. D. B. Goodman, G. Cambray, V. K. Mutalik, Y. Gao, A. P. Arkin, D. Endy, and G. M. Church. 2013. “Composability of Regulatory Sequences Controlling Transcription and Translation in Escherichia coli ,” Proceedings of the National Academy of Sciences USA 110 , 14024–29. DOI: 10.1073/pnas.1301301110.