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Description
Mono- and binuclear non-heme iron sites in proteins serve as efficient catalysts of a broad set of oxidation reactions, including activation of unreactive C–H bonds of organic substrates for subsequent desaturation, hydroxylation, halogenation, peroxidation, etc. A prominent example of such class of enzymes is the soluble O2-dependent binuclear non-heme iron enzyme Δ9-desaturase (Δ9D), evolved for the conversion of stearoyl acid to oleic acid as a part of the fatty-acid metabolic pathway of plants. Herein, we build on a detailed investigation of initial stages of O2 activation in the Δ9D active site reported earlier by our group[1,2] to probe several reaction pathways to complete the catalytic cycle, employing the hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. As a result, the activation of P intermediate via electron-proton transfer (Figure 1) is the most likely mechanism with respect to C10‒H and C9‒H bonds cleavages. At last, the energetics of key reaction steps were carefully examined at the level of advanced multi-configurational methods, allowing for the clarification of Δ9D selectivity toward desaturation (at the expense of thermodynamically more favored hydroxylation).
