한빛사 논문
Juhan Kima,b,1, Jake J. Flooda,b,1, Michael R. Kristoficha,b, Cyrus Gidfara,b, Andrew B. Morgenthalera,b, Tobias Fuhrerc, Uwe Sauerc, Daniel Snyderd, Vaughn S. Cooperd, Christopher C. Ebmeiera, William M. Olda, and Shelley D. Copleya,b,2
a Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309; b Cooperative Institute for Research in Environmental Sciences, University of Colorado Boulder, Boulder, CO 80309; c Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland; and d Center for Evolutionary Biology and Medicine, University of Pittsburgh, Pittsburgh, PA 15260
1 J.K. and J.J.F. contributed equally to this work.
2 To whom correspondence may be addressed.
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.
experimental evolution, serendipitous pathway, promiscuity, pyridoxal 5′-phosphate, metabolism
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