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

He, Hai; Gómez-Coronado, Paul A.; Zarzycki, Jan; Barthel, Sebastian; Kahnt, Jörg; Claus, Peter; Klein, Moritz; Klose, Melanie; de Crécy-Lagard, Valérie; Schindler, Daniel; Paczia, Nicole; Glatter, Timo; Erb, Tobias J.

doi:10.1038/s41467-024-53156-x

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

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He, Hai
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

Gómez-Coronado, Paul A.
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Zarzycki, Jan
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

Barthel, Sebastian
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons254414

Kahnt, Jörg
Core Facility Mass Spectrometry and Proteomics, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons254194

Claus, Peter
Core Facility Metabolomics and small Molecules Mass Spectrometry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

Klein, Moritz
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

Klose, Melanie
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons261244

Schindler, Daniel
Core Facility MPG MAXGenesys DNAfoundry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons261240

Paczia, Nicole
Core Facility Metabolomics and small Molecules Mass Spectrometry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons261236

Glatter, Timo
Core Facility Mass Spectrometry and Proteomics, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

/persons/resource/persons254247

Erb, Tobias J.
Cellular Operating Systems, Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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https://doi.org/10.1038/s41467-024-53156-x
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Citation

He, H., Gómez-Coronado, P. A., Zarzycki, J., Barthel, S., Kahnt, J., Claus, P., et al. (2024). Adaptive laboratory evolution recruits the promiscuity of succinate semialdehyde dehydrogenase to repair different metabolic deficiencies. Nature Communications, 15(1): 8898. doi:10.1038/s41467-024-53156-x.

Cite as: https://hdl.handle.net/21.11116/0000-000F-F4A6-2

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.