Professor Andrew Munro
Research in my laboratory focuses on enzymes (nature's catalysts) relevant to human health/biotechnology. Current projects include human enzymes involved in apoptosis (the process of programmed cell death by which an organism develops normally - but which also fails to function normally in cancers) and in microRNA synthesis (microRNAs are novel molecules pivotal for regulating protein synthesis, and implicated in several human diseases). This research aims to understand the structure and function of target enzymes in order to enable therapeutic strategies. Another major programme of research relates to characterization of drug target enzymes in the human pathogen Mycobacterium tuberculosis (which causes TB). We are investigating several enzymes involved in e.g. use of host cholesterol for bacterial survival in infected patients, and in reactions crucial to the synthesis of the bacterial membrane. Work aims to understand target enzyme structure and to develop novel drugs to inhibit them – with multidrug resistant TB now a “global emergency” (World Health Organization). Other biotechnologically orientated research exploits enzymes termed cytochromes P450 (P450s) to generate high value chemicals, using the exquisite ability of P450s to insert oxygen atoms at precise positions in relevant molecules. Research is supported by both UK research council and industrial sponsors.
- Bui SH, McLean KJ, Cheesman MR, Bradley JM, Rigby SEJ, Levy CW, Leys D, Munro AW. (2012). Unusual spectroscopic and ligand binding properties of the cytochrome P450-flavodoxin fusion enzyme XplA. Journal of Biological Chemistry, 287(23), 19699-19714. eScholarID:161317 | DOI:10.1074/jbc.M111.319202
- Hudson SA, McLean KJ, Surade S, Yang YQ, Leys D, Ciulli A, Munro AW, Abell C. (2012). Application of Fragment Screening and Merging to the Discovery of Inhibitors of the Mycobacterium tuberculosis Cytochrome P450 CYP121. Angewandte Chemie International Edition, 51(37), 9311-9316. eScholarID:175752 | DOI:10.1002/anie.201202544
- McLean KJ, Lafite P, Levy C, Cheesman MR, Mast N, Pikuleva IA, Leys D, Munro AW. (2009). The Structure of Mycobacterium tuberculosis CYP125 : MOLECULAR BASIS FOR CHOLESTEROL BINDING IN A P450 NEEDED FOR HOST INFECTION. Journal of Biological Chemistry, 284(51), 35524-35533. eScholarID:67178 | DOI:10.1074/jbc.M109.032706
- McLean KJ, Carroll P, Lewis DG, Dunford AJ, Seward HE, Neeli R, Cheesman MR, Marsollier L, Douglas P, Smith WE, Rosenkrands I, Cole ST, Leys D, Parish T, Munro AW. (2008). Characterization of active site structure in CYP121. A cytochrome P450 essential for viability of Mycobacterium tuberculosis H37Rv. Journal of Biological Chemistry, 283(48), 33406-33416. eScholarID:1c8300 | DOI:10.1074/jbc.M802115200