Dépôt numérique

Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase

Kumar, Pravindra; Mohammadi, Mahmood; Dhindwal, Sonali; Pham, Thi Thanh My; Bolin, Jeffrey T. et Sylvestre, Michel (2012). Structural insights into the metabolism of 2-chlorodibenzofuran by an evolved biphenyl dioxygenase Biochemical and Biophysical Research Communications , vol. 421 , nº 4. pp. 757-762. DOI: 10.1016/j.bbrc.2012.04.078.

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The biphenyl dioxygenase of Burkholderia xenovorans LB400 (BphAE LB400) is a Rieske-type oxygenase that catalyzes the stereospecific oxygenation of many heterocyclic aromatics including dibenzofuran. In a previous work, we evolved BphAE LB400 and obtained BphAE RR41. This variant metabolizes dibenzofuran and 2-chlorodibenzofuran more efficiently than BphAE LB400. However, the regiospecificity of BphAE RR41 toward these substrates differs. Dibenzofuran is metabolized principally through a lateral dioxygenation whereas 2-chlorodibenzofuran is metabolized principally through an angular dioxygenation. In order to explain this difference, we examined the crystal structures of both substrate-bound forms of BphAE RR41 obtained under anaerobic conditions. This structure analysis, in combination with biochemical data for a Ser283Gly mutant provided evidences that the substrate is compelled to move after oxygen-binding in BphAE RR41:dibenzofuran. In BphAE RR41:2-chlorodibenzofuran, the chlorine atom is close to the side chain of Ser283. This contact is missing in the BphAE RR41:dibenzofuran, and strong enough in the BphAE RR41:2-chlorodibenzofuran to help prevent substrate movement during the catalytic reaction.

Type de document: Article
Mots-clés libres: Rieske-type oxygenase; Directed evolution; Burkholderia xenovorans; LB400; Chlorodibenzofurans; Biocatalysis; Enzyme engineering
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 09 mars 2024 15:57
Dernière modification: 09 mars 2024 15:57
URI: https://espace.inrs.ca/id/eprint/14047

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