1. Hidden resources in the Escherichia coli genome restore PLP synthesis and robust growth after deletion of the essential gene pdxB
- Author
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Andrew B. Morgenthaler, Tobias Fuhrer, Jake J. Flood, Cyrus Gidfar, Vaughn S. Cooper, Michael R. Kristofich, Christopher C. Ebmeier, Daniel J. Snyder, Juhan Kim, William M. Old, Uwe Sauer, and Shelley D. Copley more...
- Subjects
Patched ,Pyridoxal ,Evolution ,pyridoxal 5′-phosphate ,Dehydrogenase ,medicine.disease_cause ,Cofactor ,Serendipitous pathway ,03 medical and health sciences ,Escherichia coli ,medicine ,Gene ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Genes, Essential ,Multidisciplinary ,biology ,030306 microbiology ,Escherichia coli Proteins ,Gene Expression Regulation, Bacterial ,Biological Sciences ,Promiscuity ,5 '-phosphate ,Experimental evolution ,Metabolism ,Glucose ,Enzyme ,Biochemistry ,chemistry ,Essential gene ,Pyridoxal Phosphate ,Mutation ,biology.protein ,Alternative complement pathway ,Carbohydrate Dehydrogenases ,Directed Molecular Evolution ,Microorganisms, Genetically-Modified ,Carrier Proteins ,Genome, Bacterial ,Metabolic Networks and Pathways - Abstract
PdxB (erythronate 4-phosphate dehydrogenase) is expected to be required for synthesis of the essential cofactor pyridoxal 5′-phosphate (PLP) in Escherichia coli. Surprisingly, incubation of the ∆pdxB strain in medium containing glucose as a sole carbon source for 10 d resulted in visible turbidity, suggesting that PLP is being produced by some alternative pathway. Continued evolution of parallel lineages for 110 to 150 generations produced several strains that grow robustly in glucose. We identified a 4-step bypass pathway patched together from promiscuous enzymes that restores PLP synthesis in strain JK1. None of the mutations in JK1 occurs in a gene encoding an enzyme in the new pathway. Two mutations indirectly enhance the ability of SerA (3-phosphoglycerate dehydrogenase) to perform a new function in the bypass pathway. Another disrupts a gene encoding a PLP phosphatase, thus preserving PLP levels. These results demonstrate that a functional pathway can be patched together from promiscuous enzymes in the proteome, even without mutations in the genes encoding those enzymes., Proceedings of the National Academy of Sciences of the United States of America, 116 (48), ISSN:0027-8424, ISSN:1091-6490 more...
- Published
- 2019
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