Adaptive laboratory evolution recruits the promiscuity of succinate semialdehyde dehydrogenase to repair different metabolic deficiencies

Hai He (), Paul A. Gómez-Coronado, Jan Zarzycki, Sebastian Barthel, Jörg Kahnt, Peter Claus, Moritz Klein, Melanie Klose, Valérie Crécy-Lagard, Daniel Schindler, Nicole Paczia, Timo Glatter and Tobias J. Erb ()
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Hai He: Max Planck Institute for Terrestrial Microbiology
Paul A. Gómez-Coronado: Max Planck Institute for Terrestrial Microbiology
Jan Zarzycki: Max Planck Institute for Terrestrial Microbiology
Sebastian Barthel: Max Planck Institute for Terrestrial Microbiology
Jörg Kahnt: Max Planck Institute for Terrestrial Microbiology
Peter Claus: Max Planck Institute for Terrestrial Microbiology
Moritz Klein: Max Planck Institute for Terrestrial Microbiology
Melanie Klose: Max Planck Institute for Terrestrial Microbiology
Valérie Crécy-Lagard: University of Florida
Daniel Schindler: Max Planck Institute for Terrestrial Microbiology
Nicole Paczia: Max Planck Institute for Terrestrial Microbiology
Timo Glatter: Max Planck Institute for Terrestrial Microbiology
Tobias J. Erb: Max Planck Institute for Terrestrial Microbiology

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

Abstract: Abstract Promiscuous enzymes often serve as the starting point for the evolution of novel functions. Yet, the extent to which the promiscuity of an individual enzyme can be harnessed several times independently for different purposes during evolution is poorly reported. Here, we present a case study illustrating how NAD(P)+-dependent succinate semialdehyde dehydrogenase of Escherichia coli (Sad) is independently recruited through various evolutionary mechanisms for distinct metabolic demands, in particular vitamin biosynthesis and central carbon metabolism. Using adaptive laboratory evolution (ALE), we show that Sad can substitute for the roles of erythrose 4-phosphate dehydrogenase in pyridoxal 5’-phosphate (PLP) biosynthesis and glyceraldehyde 3-phosphate dehydrogenase in glycolysis. To recruit Sad for PLP biosynthesis and glycolysis, ALE employs various mechanisms, including active site mutation, copy number amplification, and (de)regulation of gene expression. Our study traces down these different evolutionary trajectories, reports on the surprising active site plasticity of Sad, identifies regulatory links in amino acid metabolism, and highlights the potential of an ordinary enzyme as innovation reservoir for evolution.

Date: 2024
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DOI: 10.1038/s41467-024-53156-x

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