Philip Olivares graduated from Michigan Technological University with a B.S. in Pharmaceutical Chemistry in spring 2013. During his undergraduate career, he aided in the research of three labs: an analytical atmospheric chemistry lab lead by Dr. Lynn Mazzoleni, a forestry lab under the guidance of Dr. Yinan Yuan, and a biochemistry lab lead by Dr. Pushpalatha Murthy focusing on improving heterologous expression of an alkaline phytase with ability to decrease soil phosphate loading, and thus decrease likelyhood of algal blooms when used as a feed stock additive.
His graduate research experience started the following fall in Dr. Satish Nair’s lab in the Biochemistry department focusing on structural studies of enzymes and receptors involved in natural product regulation and biosynthesis using X-ray crystallography. This structural work focuses on a class of natural product regulatory receptors in Streptomyces called gamma-butyrolactone (GBL) receptors working to better understand this structurally neglected class. These receptors are known regulators of many pharmaceutically relevant drugs including streptomycin, and a large number of uncharacterized biosynthetic gene clusters.
Structural and Biochemical Studies of Psf3,
a Reductase Involved in Fosfomycin Biosynthesis
Fosfomycin, a broad-spectrum phosphonate antibiotic often used fo the treatment of urinary, and other gastrointestinal infections. This drug acts as a phosphoenol pyruvate (PEP) analog in order to block peptidoglycan biosynthesis via inhibition of MurA, a UDP-GlcNAc enolpyruval transferase. Psf3 is a stereospecific carbonyl reductase involved in the penultimate step of fosfomycin biosynthesis in Pseudomonas syringae. Cocrystals of Psf3, NADP+ and 2-OPP diffracted to a resolution of 2.2 angstroms, suggesting a water-mediated mechanism of action, and deepening the knowledge pool of phosphonate biosynthetic enzymes.