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Underground isoleucine biosynthesis pathways in E. coli

MPG-Autoren
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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;

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

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

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

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

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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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Zitation

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.


Zitierlink: https://hdl.handle.net/21.11116/0000-0007-0058-6
Zusammenfassung
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.