Albert Bowers received his PhD in organic chemistry (synthetic methods) from the University of Illinois at Chicago. He carried out postdoctoral research (total synthesis) at Colorado State University before moving as an NIH sponsored fellow to Harvard Medical School (biosynthesis). He is a member of the UNC Lineberger Comprehensive Cancer Center and and affiliate member of the Center for Integrative Chemical Biology and Drug Discovery.
Key words: Natural products medicinal chemistry, combinatorial synthesis and biosynthesis, structure-based drug design and mode of action.
Research in our lab is concentrated on the synthesis, assessment, and modification of potential therapeutic leads, especially those derived from natural products. We use chemical synthesis as well as genetic manipulation of the natural biosyntheses to access and modify compounds to study structure-activity relationships (SAR). These efforts involves the integration of basic concepts in organic reaction mechanisms, synthetic organic chemistry, biochemistry, molecular biology, bioinformatics and computational chemistry.
A major focus of the lab is using genetic information about natural product biosynthesis to manipulate pathways, create new compounds, and rationally modify or improve their pharmacology. This has the benefit of efficiently accessing complex natural-product-like structures without the need for step-wise synthesis chemical synthesis. In particular, we are engineering several exceptionally promiscuous enzymatic pathways to make modified versions of their endogenous products with new biological activities. We have had success in targeting libraries of these engineered compounds against a number of challenging but important cancer targets. A mechanistic understanding of these pathways is also allowing us to expand on the endogenous structures by incorporating unnatural functional groups, capable of reacting in parallel. Additionally, we are exploring the ability to express the engineered pathways in presence of potential targets in order to ‘evolve’ new natural-product-like inhibitors.
Recycling Natural Products
Our laboratory also actively pursues SAR of several natural products by means of chemical synthesis. A number of natural products have been ignored clinically (as well as industrially) due to fundamental shortcomings, such as poor solubility or excessive cytotoxicity. Research in the lab is aimed at removing these impediments to clinical relevance by developing efficient syntheses of proposed active fragments and investigations of the minimal basis for their activity. Compounds currently being worked on in the lab target multidrug resistant venereal infection (gonorrhea and chlamydia) and aberrant gene regulation involved in cancer progression.
Elicitation and Characterization of New Natural Products
Most bacterial genomes have the potential to produce many more, potentially-therapeutic natural products than have been isolated to date. We work with collaborators here at UNC and at peer institutions to elicit or turn on these unknown biosynthetic pathways and characterize their products.
Education, Certification and Licensure
- Visiting Scholar, National Institutes of Health, Bethesda, Maryland
- PhD in Organic Chemistry, University of Illinois at Chicago, 2007
- Visiting Scholar, Kyoto University, Kyoto, Japan, 2005
- BA in Art History, University of Chicago, 2001
- W. J. Wever, J. W. Bogart, J. A. Bacile, A. N. Chan, F. C. Schroeder, and A. A. Bowers, Chemoenzymatic Synthesis of Thiazolyl Peptide Natural Products Featuring an Enzyme-Catalyzed Formal [4+2] Cycloaddition, J. Am. Chem. Soc., ASAP.
- Z. D. Dunn, W. J. Wever, N. J. Economou, A. A. Bowers, and B. Li, Enzymatic Basis of ‘Hybridity’ in Thiomarinol Biosynthesis, Angew. Chem. Int. Ed., Early View.
- R. M. Bleich, J. D. Watrous, P. C. Dorrestein, A. A. Bowers, E. A. Shank, Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis, Proc. Nat. Acad. Sci. USA, 112, 3086-91, 2015.
- B. Li, W. J. Wever, C. T. Walsh, A. A. Bowers, Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics, Nat. Prod. Rep., 31, 905-23, 2014.
- X. Du, D. Wojtowicz, A. A. Bowers, D. Levens, C. Benham, and T. M. Przytycka Genome-wide distribution of non-B DNA motifs is shaped by operon structure and suggests transcriptional importance of non-B DNA structures inEscherichia coli, Nuc. Acid. Res, 41, 5965-5977, 2013.
- W. Wever, M. A. Cinelli, A. A. Bowers, Visible Light Mediated Activation and O-Glycosylation of Thioglycosides, Org. Lett., 15(1), 30-33, 2013.
- Arnison, P. et al., Ribosomally Synthesized and Post-Translationally Modified Peptide Natural Products: Overview and Recommendations for a Universal Nomenclature, Nat. Prod. Rep., 30, 108-160, 2013.
- A. A. Bowers, Preparation of natural product-like cyclic peptide libraries, MedChemComm, 3, 905-915 2012.
- B. Li, R. R. Forseth, A. A. Bowers, F. C. Schroeder, C. T. Walsh, A Backup Plan for Self-protection: S-Methylation of Holomycin Biosynthetic Intermediates in Streptomyces clavuligerus, ChemBioChem, 13(17) 2521-2526, 2012.
- A. A. Bowers, M. G. Acker, T. S. Young, and C. T. Walsh, Generation of Thiocillin Ring Size Variants by Prepeptide Gene Replacement and In Vivo Processing by Bacillus cereus, J. Am. Chem. Soc., 134(25) 10313-10316, 2012.