Trends in Biotechnology
Volume 19, Issue 12, 1 December 2001, Pages 482-486
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Research update
Small-molecule metabolism: an enzyme mosaic

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Abstract

Escherichia coli has been a popular organism for studying metabolic pathways. In an attempt to find out more about how these pathways are constructed, the enzymes were analysed by defining their protein domains. Structural assignments and sequence comparisons were used to show that 213 domain families constitute ∼90% of the enzymes in the small-molecule metabolic pathways. Catalytic or cofactor-binding properties between family members are often conserved, while recognition of the main substrate with change in catalytic mechanism is only observed in a few cases of consecutive enzymes in a pathway. Recruitment of domains across pathways is very common, but there is little regularity in the pattern of domains in metabolic pathways. This is analogous to a mosaic in which a stone of a certain colour is selected to fill a position in the picture.

Section snippets

Structural anatomy of E. coli small-molecule metabolic enzymes

The metabolic pathways in E. coli are probably the most thoroughly studied of any organism. Although the details of the enzymes and metabolic pathways will differ from organism to organism, the principles of the structure and evolution of the pathways would be expected to apply across all organisms. The EcoCyc database 1 contains comprehensive information on small-molecule metabolism in E. coli, and the 106 pathways and the corresponding 581 enzymes described in this database were used in the

Evolution of E. coli small-molecule metabolic pathways

Information about the domain structures of the individual enzymes can be used to investigate aspects of the evolution of metabolic pathways. Of the 213 domain families, 144 have members distributed across different pathways. The 69 families that are active in only one pathway are all small: 67 have one or two members, one has three members and one has four members. This distribution shows that the evolution of metabolic pathways involved widespread recruitment of enzymes to different pathways,

Conclusions and discussion

This description of how a relatively small repertoire of 213 domain families constitutes 90% of the enzymes in the E. coli small-molecule metabolic pathways is, to some extent, paradoxical. Although the SMM enzymes have arisen by extensive duplication, with an average of 3.4 domain members per SMM family, the distribution of families within and across pathways is complex: there is little repetition of domains in consecutive steps of pathways and little serial homology across pathways. Together

Acknowledgements

SAT has a Beit Memorial Fellowship. SCGR acknowledges support from GlaxoSmithkline and MR acknowledges support from the NIH and the NASA Astrobiology Institute. The authors acknowledge computational support from the BBSRC.

References (12)

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