Nigel Priestly

Nigel D. Priestley
Professor

Email: nigel.priestley@umontana.edu

Phone: (406) 243-6251

Lab: (406) 243-6096

Nigel Priestley came to the University of Montana in 1999 from the Ohio State University.  He earned his Ph.D. from The University of Southampton, UK in 1991.  While at Ohio State University he was an Assistant Professor in the Division of Medicinal Chemistry and Pharmacognosy.

 

Links of Interest

Priestley Group

Research Interests

Our group interests are firmly rooted in natural product chemistry, biochemistry, and biosynthesis. The unifying theme of our researchis to gain an understanding of how natural products are made so that the organisms that produce them can be manipulated to produce 'non-natural' natural products.

Nonactin is a macrocyclic polyether ionophore antibiotic. The structure is a tetramer composed of two monomers of(+)-nonactic acid and two monomers of (-)-nonactic acid. We are currently making new analogs of nonactin by genetic engineering of the nonactin biosynthesis gene cluster and through the use of recombinant, overexpressed biosynthesis enzymes in a synergistic approach with synthetic organic chemistry. The work also encompasses the synthesis and use of stable isotope labeled precursors to elucidate the mechanism of the reactions catalyzed by the nonactate poyketide synthase.

The anthracycline compounds daunorubicin and doxorubicin are significant anti-cancer chemotherapeutics. We are studying the details of their biosynthesis which includes the chemistry catalyzed by the type II anthracycline PKS and the post-PKS modifications. Two emphases of the research are the enzymes DoxA (P450 monooxygenase) and DnmS (a glycosyl transferase) which are important enzymes catalyzing post-PKS processing steps.

Other research includes the cloning and analysis of the biosynthesis gene clusters responsible for making a number of other polyketide metabolites and the use of combinatorial methods for producing large libraries of complex, stereo-rich, potential lead structures based upon natural product scaffolds. More information on the individual research projects can be found on the personal web pages.

Representative Publications

Nikodinovic, Jasmina; Dinges, Jennifer M.; Bergmeier, Stephen C.; McMills, Mark C.; Wright, Dennis L.; Priestley, Nigel D..  Resolution of Methyl Nonactate by Rhodococcus erythropolis under Aerobic and Anaerobic Conditions.    Organic Letters     ACS ASAP.  CODEN: ORLEF7  ISSN:1523-7060.  AN 2006:39000    CAPLUS

Cox, James E.; Priestley, Nigel D..  Nonactin biosynthesis: The product of the resistance gene degrades nonactin stereospecifically to form homochiral nonactate dimers.    Journal of the American Chemical Society  (2005),  127(22),  7976-7977.  CODEN: JACSAT  ISSN:0002-7863.  CAN 143:112212  AN 2005:414342    CAPLUS

Michael E. Nelson and Nigel D. Priestley, J. Am. Chem. Soc., 2002, 124(12),2894-2902, “Nonactin biosynthesis: the initial committed step is the condensation of acetate (malonate) and succinate”

Robbie J. Walczak, Michael E. Nelson, and Nigel D. Priestley, J. Am. Chem. Soc., 2001, 123(42), 10415-10416, “Nonactin biosynthesis: disruption of the polyketide synthase genes, nonKJ, in S. griseus leads to an overall 96 % decrease in macrotetrolide production, yet a net increase in nonactin analogs which incorporate isobutyrate.”

Robbie J. Walczak, Jennifer V. Hines, William R. Strohl, and Nigel D. Priestley, Organic Letters, 2001, 3(15), 2277-2279, “Bioconversion of the anthracycline analog desacetyladriamycin by recombinant DoxA, a P450-monooxygenase from Streptomyces sp. strain C5.”

Vineet J. Rajgarhia, Nigel D. Priestley, and William R. Strohl, Metabolic Engineering, 2001, 3(1), 49-63, “The product of dpsC confers starter unit fidelity upon the daunorubicin polyketide synthase of Streptomyces sp. Strain C5.”

Robbie J. Walczak, Anton J. Woo, William R. Strohl and Nigel D. Priestley, FEMS Microbiology Letts., 2000, 183(1), 171-5, “Nonactin biosynthesis: the potential nonactin biosynthesis gene cluster contains type II polyketide synthase-like genes.”

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