Three serendipitous pathways in E. coli can bypass a block in pyridoxal‐5′‐phosphate synthesis

Molecular Systems Biology - Tập 6 Số 1 - 2010
Juhan Kim1,2, Jamie P. Kershner1,2, Yehor Y. Novikov1,2, R. L. Shoemaker3, Shelley D. Copley1,2
1Cooperative Institute for Research in Environmental Sciences, University of Colorado, Boulder, CO, USA
2Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO/USA
3Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO, USA

Tóm tắt

Bacterial genomes encode hundreds to thousands of enzymes, most of which are specialized for particular functions. However, most enzymes have inefficient promiscuous activities, as well, that generally serve no purpose. Promiscuous reactions can be patched together to form multistep metabolic pathways. Mutations that increase expression or activity of enzymes in such serendipitous pathways can elevate flux through the pathway to a physiologically significant level. In this study, we describe the discovery of three serendipitous pathways that allow synthesis of pyridoxal‐5′‐phosphate (PLP) in a strain of E. coli that lacks 4‐phosphoerythronate (4PE) dehydrogenase (PdxB) when one of seven different genes is overexpressed. We have characterized one of these pathways in detail. This pathway diverts material from serine biosynthesis and generates an intermediate in the normal PLP synthesis pathway downstream of the block caused by lack of PdxB. Steps in the pathway are catalyzed by a protein of unknown function, a broad‐specificity enzyme whose physiological role is unknown, and a promiscuous activity of an enzyme that normally serves another function. One step in the pathway may be non‐enzymatic.

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Tài liệu tham khảo

10.1016/S0167-4838(99)00216-2

10.1038/msb4100050

10.1016/0006-291X(81)91490-X

10.1038/nchembio.186

10.1111/j.1432-1033.1976.tb10186.x

10.1038/28431

10.1016/0040-4020(96)00493-0

10.1016/S0968-0004(00)01562-0

Dempsey WB, 1987, Synthesis of pyridoxal phosphate, Escherichia coli and Salmonella typhimurium; Cellular and Molecular Biology, 539

10.1016/0014-5793(93)80005-F

10.1042/bj2340049

10.1042/BJ20070765

10.1016/j.jmb.2005.04.027

10.1021/bi051681j

10.1002/pro.5560050105

10.1093/oxfordjournals.jbchem.a123427

10.1016/0006-291X(90)91157-N

10.1016/S0021-9258(18)64096-7

10.1074/jbc.271.48.30426

10.1016/S0021-9258(18)47589-8

10.1021/ja00454a058

10.1139/o73-185

10.1146/annurev.mi.30.100176.002205

10.1046/j.1365-2958.1999.01495.x

10.1006/abio.1996.0238

10.1128/JB.182.4.891-897.2000

10.1021/bi00177a035

10.1128/jb.172.11.6518-6528.1990

10.1046/j.1432-1327.1998.2550220.x

10.1073/pnas.95.5.2105

10.1007/s00018-005-5386-7

10.1021/bi049424m

10.1021/bi0506268

10.1016/j.jmb.2007.12.017

10.1021/ja983390m

10.1021/bi0028892

10.1016/j.jmb.2008.01.043

10.1093/molbev/msm204

10.1016/S0021-9258(17)42554-3

10.1128/JB.01257-06

10.1128/jb.134.3.944-949.1978

10.1006/jmra.1995.0759

10.1128/jb.116.1.341-345.1973

10.1021/bi035815

10.1016/0003-2697(87)90649-X

10.1016/0003-2697(79)90590-6

10.1021/ja0370948

10.1016/j.cbpa.2006.08.008

10.1111/j.1574-6968.1996.tb08001.x

10.1128/jb.178.1.232-239.1996