Advancing the scale of synthetic biology via cross-species transfer of cellular functions enabled by iModulon engraftment

Donghui Choe, Connor A. Olson, Richard Szubin, Hannah Yang, Jaemin Sung, Adam M. Feist and Bernhard O. Palsson ()
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Donghui Choe: University of California San Diego
Connor A. Olson: University of California San Diego
Richard Szubin: University of California San Diego
Hannah Yang: University of California San Diego
Jaemin Sung: University of California San Diego
Adam M. Feist: University of California San Diego
Bernhard O. Palsson: University of California San Diego

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes, such iModulons represent specific cellular functions. The identification of iModulons enables accurate identification of genes necessary and sufficient for cross-species transfer of cellular functions. We demonstrate cross-species transfer of: 1) the biotransformation of vanillate to protocatechuate, 2) a malonate catabolic pathway, 3) a catabolic pathway for 2,3-butanediol, and 4) an antimicrobial resistance to ampicillin found in multiple Pseudomonas species to Escherichia coli. iModulon-based engineering is a transformative strategy as it includes all genes comprising the transferred cellular function, including genes without functional annotation. Adaptive laboratory evolution was deployed to optimize the cellular function transferred, revealing mutations in the host. Combining big data analytics and laboratory evolution thus enhances the level of understanding of systems biology, and synthetic biology for strain design and development.

Date: 2024
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DOI: 10.1038/s41467-024-46486-3

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