5aii

Publication Abstract from PubMed

The epoxide hydrolases (EHs) represent an attractive option for the synthesis of chiral epoxides and 1,2-diols which are valuable building blocks for the synthesis of several pharmaceutical compounds. A metagenomic approach has been used to identify two new members of the atypical EH limonene-1,2-epoxide hydrolase (LEH) family of enzymes. These two LEHs (Tomsk-LEH and CH55-LEH) show EH activities towards different epoxide substrates, differing in most cases from those previously identified for Rhodococcus erythropolis (Re-LEH) in terms of stereoselectivity. Tomsk-LEH and CH55-LEH, both from thermophilic sources, have higher optimal temperatures and apparent melting temperatures than Re-LEH. The new LEH enzymes have been crystallized and their structures solved to high resolution in the native form and in complex with the inhibitor valpromide for Tomsk-LEH and poly(ethylene glycol) for CH55-LEH. The structural analysis has provided insights into the LEH mechanism, substrate specificity and stereoselectivity of these new LEH enzymes, which has been supported by mutagenesis studies. DATABASE: The atomic coordinates and structure factors of the crystal structures have been deposited in the Protein Data Bank with the codes 5AIF (Tomsk-LEH native structure), 5AIG (Tomsk-LEH valpromide complex), 5AIH (CH55-LEH native structure) and 5AII (CH55-LEH PEG complex). Nucleotide sequence data are available in the GenBank databases under the accession numbers KP765711 (Tomsk-LEH) and KP765710 (CH55-LEH).

Discovery and characterization of thermophilic limonene-1,2-epoxide hydrolases from hot spring metagenomic libraries.,Ferrandi EE, Sayer C, Isupov MN, Annovazzi C, Marchesi C, Iacobone G, Peng X, Bonch-Osmolovskaya E, Wohlgemuth R, Littlechild JA, Monti D FEBS J. 2015 May 29. doi: 10.1111/febs.13328. PMID:26032250^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.