Underground isoleucine biosynthesis pathways in E. coli

Cotton, C. A. R.; Bernhardsgrütter, Iria; He, H.; Burgener, Simon; Schulz, Luca; Paczia, Nicole; Dronsella, B.; Erban, A.; Toman, St.; Dempfle, M.; de Maria, A.; Kopka, J.; Lindner, S. N.; Erb, Tobias J; Bar-Even, A.

doi:10.7554/eLife.54207

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Underground isoleucine biosynthesis pathways in E. coli

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Cotton, C. A. R.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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He, H.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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Dronsella, B.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97140

Erban, A.
Applied Metabolome Analysis, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons250287

Toman, St.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons228918

Dempfle, M.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons250283

de Maria, A.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97239

Kopka, J.
Applied Metabolome Analysis, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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Lindner, S. N.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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Bar-Even, A.
Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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Citation

Cotton, C. A. R., Bernhardsgrütter, I., He, H., Burgener, S., Schulz, L., Paczia, N., et al. (2020). Underground isoleucine biosynthesis pathways in E. coli. eLife, 9: e54207. doi:10.7554/eLife.54207.

Cite as: https://hdl.handle.net/21.11116/0000-0007-0058-6

Abstract

The promiscuous activities of enzymes provide fertile ground for the evolution of new metabolic pathways. Here, we systematically explore the ability of ̑extitE. coli} to harness underground metabolism to compensate for the deletion of an essential biosynthetic pathway. By deleting all threonine deaminases, we generated a strain in which isoleucine biosynthesis was interrupted at the level of 2-ketobutyrate. Incubation of this strain under aerobic conditions resulted in the emergence of a novel 2-ketobutyrate biosynthesis pathway based upon the promiscuous cleavage of ̑extit{O-succinyl-L-homoserine by cystathionine γ-synthase (MetB). Under anaerobic conditions, pyruvate formate-lyase enabled 2-ketobutyrate biosynthesis from propionyl-CoA and formate. Surprisingly, we found this anaerobic route to provide a substantial fraction of isoleucine in a WT strain, when propionate is available in the medium. This study demonstrates the selective advantage underground metabolism offers, providing metabolic redundancy and flexibility which allow for the best use of environmental carbon sources.