Metagenomic mining of regulatory elements enables programmable species-selective gene expression
Author(s)Johns, Nathan I; Yim, Sung Sun; Blazejewski, Tomasz; Dias Gomes, Antonio; Yang, Anthony; Smillie, Chris S; Smith, Mark Burnham; Alm, Eric J; Kosuri, Sriram; Wang, Harris H; ... Show more Show less
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Robust and predictably performing synthetic circuits rely on the use of well-characterized regulatory parts across different genetic backgrounds and environmental contexts. Here we report the large-scale metagenomic mining of thousands of natural 5′ regulatory sequences from diverse bacteria, and their multiplexed gene expression characterization in industrially relevant microbes. We identified sequences with broad and host-specific expression properties that are robust in various growth conditions. We also observed substantial differences between species in terms of their capacity to utilize exogenous regulatory sequences. Finally, we demonstrate programmable species-selective gene expression that produces distinct and diverse output patterns in different microbes. Together, these findings provide a rich resource of characterized natural regulatory sequences and a framework that can be used to engineer synthetic gene circuits with unique and tunable cross-species functionality and properties, and also suggest the prospect of ultimately engineering complex behaviors at the community level.
DepartmentInstitute for Medical Engineering and Science; Massachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Civil and Environmental Engineering; Massachusetts Institute of Technology. Department of Mathematics; Massachusetts Institute of Technology. Department of Physics
Johns, Nathan I, Antonio L C Gomes, Sung Sun Yim, Anthony Yang, Tomasz Blazejewski, Christopher S Smillie, Mark B Smith, Eric J Alm, Sriram Kosuri, and Harris H Wang. “Metagenomic Mining of Regulatory Elements Enables Programmable Species-Selective Gene Expression.” Nature Methods 15, no. 5 (March 19, 2018): 323–329.
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