PMID:21332126
| Citation |
Khersonsky, O, Malitsky, S, Rogachev, I and Tawfik, DS (2011) Role of chemistry versus substrate binding in recruiting promiscuous enzyme functions. Biochemistry 50:2683-90 |
|---|---|
| Abstract |
Two different scenarios for the recruitment of evolutionary starting points and their subsequent divergence to give new enzymes have been described. The coincidental, promiscuous starting activity may regard the same reaction chemistry on a new substrate (substrate ambiguity). Alternatively, substrate binding guides the recruitment of an enzyme whose reaction chemistry differs from that of the newly evolving one (catalytic promiscuity). While substrate ambiguity seems to underlie the divergence of most enzyme families, the relative levels of occurrence of these scenarios remain unknown. Screening the Escherichia coli proteome with a comparative series of xenobiotic substrates, we found that substrate ambiguity was, as anticipated, more frequent than reaction promiscuity. However, for at least one unnatural reaction (phosphonoesterase), a promiscuous enzyme was identified only when the substrate was decorated with the naturally abundant phosphate group. These findings support the prevailing hypothesis of chemistry-driven divergence but also suggest that recognition of familiar substrate motifs plays a role. In the absence of enzymes catalyzing the same chemistry, having a familiar, naturally occurring substrate motif (chemophore) such as phosphate may increase the likelihood of catalytic promiscuity. Chemophore anchoring may also find practical applications in identifying catalysts for unnatural reactions. |
| Links |
PubMed Online version:10.1021/bi101763c |
| Keywords |
Biocatalysis; Escherichia coli K12/enzymology; Escherichia coli K12/genetics; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Evolution, Molecular; Proteome/metabolism; Substrate Specificity; Xenobiotics/chemistry; Xenobiotics/metabolism |
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