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Rachel Austin

Rachel Austin

Student Invited Lecture
Wed, Feb. 12, 2020, 4:30pm
Edward C Taylor Auditorium, Frick B02
Host: G.S.O. & The Groves Lab

Catalytic activity of non-heme diiron alkane monooxygenases

Alkane hydroxylase (AlkB) is a membrane-spanning non-heme diiron enzyme with a histidine-rich coordination site, first identified 50 years ago[1], responsible for catalyzing the hydroxylation of the majority of medium-to-long straight chain alkanes in the environment. AlkB catalyzes the hydroxylation of terminal alkanes, the epoxidation of alkenes, and, in selected cases, the desaturation of alkanes.  Despite its importance in the global carbon cycle, relatively little is known about this large and widely-distributed class of hydroxylases.  We have studied the reaction mechanism and substrate specificity of AlkB from Pseudomonas putida GPo1.  More recently we have expressed, purified, and characterized the catalytic activity of AlkB from 5 additional organisms:  the marine organism Alcanivorax borkumensis AP1, Dietzea cinnamea, Thermomonospora curvata, Mycobacterium tuberculosis, and Fontimonas thermophila.  In addition, we are studying the catalytic activity of two structurally-related enzymes: xylene monooxyganse and UndBFunctional studies on these non-heme diiron hydroxylases, interpreted in light of recently published crystal structures of two related enzymes, the fatty acid desaturase steroyl-CoA desaturase[2][3] and sphingolipid a-hydroxylase (Scs7p), a yeast homolog of fatty acid 2-hydroxylase (FA2H)[4], answer some questions about structure-function relationships in this important class of metalloenzymes and raise others. 


[1] McKenna, Eva J.; Coon, Minor J. (1970) Enzymatic -Oxidation, Journal of Biological Chemistry, 245, 3882-3889.

[2] Bai, Y., McCoy, J. G., Levin, E. J., Sobrado, P., Rajashankar, K. R., Fox, B. G., and Zhou, M. (2015) X-ray structure of a mammalian stearoyl-CoA desaturase. Nature 524, 252–256

[3] Wang, H., Klein, M. G., Zou, H., Lane, W., Snell, G., Levin, I., Li, K., and Sang, B. C. (2015) Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate. Nat. Struct. Mol. Biol. 22, 581–585

[4] Guangyu Zhu, Mary Koszelak-Rosenblum, Sara M. Connelly, Mark E. Dumont, and Michael G. Malkowski (2015) The Crystal Structure of an Integral Membrane Fatty Acid a-Hydroxylase, J. Biol. Chem. 290, 29820-29833