Topic: Oxidative Reactions in Biology: from Atoms to Organelles

Speaker: Professor Denis Proshlyakov - Michigan State University

Date: Thursday, August 15, 2019

Time: 4:10 PM

Location: 136 CEM

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Michigan State University — Department of Chemistry

Oxidative Reactions in Biology: from Atoms to Organelles



Abstract:  Since the Cambrian explosion, molecular oxygen sustains aerobic life. Heme-based O2 chemistry has been mostly established owing to the predictable coordination and strong optical absorption of porphyrin. Less is known about the flexible and diverse active sites of mono- and di-nuclear non-heme iron enzymes, which use vibrant and often elusive intermediates to perform intriguing transformations. Our Raman studies on Fe dioxygenase TauD revealed a novel, alkoxyl-mediated oxygenation mechanism via an FeIII=O intermediate. Investigation of this controversial species by FTIR spectro-electrochemistry with heterogeneous kinetic modeling uncovered a dramatic, reversible, redox-linked tuning in TauD of up to 0.5V. This finding challenges the prevailing view of a static protein moiety that mostly positions the substrate. It shows that protein can play a dynamic role in the reactivity of the oxygen species during redox reactions.

Even greater chemical diversity is found in di-nuclear Fe active sites. Intermediate Q of methane monooxygenase, the strongest known biological oxidant, activates the C-H bond of methane using an FeIV-(m2-O)2-FeIV core. Aldehyde deformylating oxygenase uses a similar metal cluster to generate an FeIII-m-1,1-O2-FeIII species during oxidative decarboxylation of fatty aldehydes to alkanes/alkenes. The vibrational structure of this unique intermediate has been recently resolved by our group.

Analytical methods that evolved from our basic studies on metalloenzymes paved the way for the development of the next generation approach to study the supramolecular complexes of electron transport chains (ETC). Even minor malfunctions of the mitochondrial ETC can lead to pathologies of high socioeconomic impact (diabetes, cardiovascular and neurological disorders). We demonstrate, for the first time, that electrochemical manipulation of the ETC in intact mitochondria yields quantitative and specific information about individual complexes in their native environments on sub-microliter scales. This method can revolutionize basic and applied clinical studies on metabolic disorders, opening exciting opportunities beyond bio-mimetic electrochemistry, such as previously unattainable transient and sustained studies on organelles, whole cells, tissues, and organoids, including investigation of their redox states using an in situ Raman spectroscopy.

*Please see by the Chemistry elevators for the full abstract with pictures.



Room 136 Chemistry