Hidden resources in bacterial proteomes fuel metabolic innovation

15 October 2021

Shelley Copley
Molecular, Cellular and Developmental Biology
University of Colorado Boulder

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Abstract

The evolution of new metabolic pathways has been a driver of diversification from the last universal common ancestor 3.8 billion years ago to the present. Bioinformatic evidence suggests that many pathways were assembled by recruiting promiscuous enzymes to serve new functions. However, the processes by which new pathways have emerged are lost in time. We have little information about the environmental conditions that fostered emergence of new pathways, the genome context in which new pathways emerged, and the types of mutations that elevated flux through inefficient new pathways. Experimental laboratory evolution allows us to address these questions. We have identified a novel four-step pathway that allows E. coli to bypass a block in the pathway for synthesis in PLP, an essential cofactor, and have identified the mechanisms by which critical mutations enabled this pathway to reconstitute PLP synthesis. This is not the only solution to the problem, however. After deleting genes involved in the novel pathway, we have evolved strains that have come up with other solutions. Other bacteria also seem to evolve other solutions, likely because they have different promiscuous activities available in their proteomes. These studies reveal the evolutionary potential that resides in the vast reservoir of promiscuous activities in any proteome.

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