Paul Straight

Research Interests:

Microbial Interactions and Secondary Metabolism

Microorganisms produce the majority of our antibiotics, antifungal, antiviral, and anticancer therapeutics. Yet, these natural product medicines represent only a small fraction of the chemically diverse small molecules produced primarily by bacteria and fungi. The functions of such compounds in microbial communities are sure to be as diverse as the chemical structures themselves, although little is known beyond a handful of examples. Our laboratory studies the function of small molecules as chemical signals in the microbial world. We focus on the interactions between different species of bacteria in co-culture to understand how diverse chemical signals are synthesized and perceived.

Our goal is to understand how microorganisms interact in complex communities. Specifically, we study how small molecules produced in a microbial community affect the growth, development and metabolic output of the organisms. We use a combination of microbiology, genetic, genomic, and biochemical approaches to dissect complex interspecies interactions. Currently, our research focuses on the interactions of the soil bacteria Bacillus subtilis and members of the genus Streptomyces, known for their prolific production of bioactive small molecules and development of aerial structures and spores.

Microbial developmental processes are particularly attuned to environmental signals, including those generated by neighboring organisms. In one area of research interest, we investigate developmental interactions between bacteria in order to probe the mode of action of small molecules beyond a query of antibiotic activity. As a second area of interest, we study the regulation and assembly of the enzymatic machinery for small molecule synthesis and export by the producer cell. To synthesize low molecular weight compounds of precise chemical structure, microorganisms use protein enzymatic complexes that are often larger than the ribosome. The energy invested in producing these synthases underscores the importance of the compounds in environmentally relevant settings. Understanding the activity and synthesis of microbial small molecules will help us predict the outcome of complex interactions in natural environments and will highlight strategies for discovery of new therapeutics and new therapeutic targets.

Selected Publications:

Yang, Y.L., Xu, Y., Straight, P., and Dorrestein, P.C. 2009. Translating metabolic exchange with imaging mass spectrometry. Nat Chem Biol 5: 885-887.

Straight, P.D. and Kolter, R. 2009. Interspecies chemical communication in bacterial development. Annu Rev Microbiol 63: 99-118.

Yin, J., Straight, P.D., Hrvatin, S., Dorrestein, P.C., Bumpus, S.B., Jao, C., Kelleher, N.L., Kolter, R., and Walsh, C.T. 2007. Genome-wide high-throughput mining of natural-product biosynthetic gene clusters by phage display. Chem Biol 14: 303-312.

Butcher, R.A., Schroeder, F.C., Fischbach, M.A., Straight, P.D., Kolter, R., Walsh, C.T., and Clardy, J. 2007. The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis. Proc Natl Acad Sci U S A 104: 1506-1509.

Straight, P.D., Fischbach, M.A., Walsh, C.T., Rudner, D.Z., and Kolter, R. 2007. A singular enzymatic megacomplex from Bacillus subtilis. Proc Natl Acad Sci U S A 104: 305-310.

Dorrestein, P.C., Bumpus, S.B., Calderone, C.T., Garneau-Tsodikova, S., Aron, Z.D., Straight, P.D., Kolter, R., Walsh, C.T., and Kelleher, N.L. 2006. Facile detection of acyl and peptidyl intermediates on thiotemplate carrier domains via phosphopantetheinyl elimination reactions during tandem mass spectrometry. Biochemistry 45: 12756-12766.

Straight, P.D., Willey, J.M., and Kolter, R. 2006. Interactions between Streptomyces coelicolor and Bacillus subtilis: Role of surfactants in raising aerial structures. J Bacteriol 188: 4918-4925.

Dorrestein, P.C., Blackhall, J., Straight, P.D., Fischbach, M.A., Garneau-Tsodikova, S., Edwards, D.J., McLaughlin, S., Lin, M., Gerwick, W.H., Kolter, R. et al. 2006. Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry. Biochemistry 45: 1537-1546.

Yin, J., Straight, P.D., McLoughlin, S.M., Zhou, Z., Lin, A.J., Golan, D.E., Kelleher, N.L., Kolter, R., and Walsh, C.T. 2005. Genetically encoded short peptide tag for versatile protein labeling by Sfp phosphopantetheinyl transferase. Proc Natl Acad Sci U S A 102: 15815-15820.

Winey, M., Morgan, G.P., Straight, P.D., Giddings, T.H., Jr., and Mastronarde, D.N. 2005. Three-dimensional ultrastructure of Saccharomyces cerevisiae meiotic spindles. Mol Biol Cell 16: 1178-1188.

Straight, P.D., Giddings, T.H., Jr., and Winey, M. 2000. Mps1p regulates meiotic spindle pole body duplication in addition to having novel roles during sporulation. Mol Biol Cell 11: 3525-3537.

Wolfsberg, T.G., Straight, P.D., Gerena, R.L., Huovila, A.P., Primakoff, P., Myles, D.G., and White, J.M. 1995. ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain. Dev Biol 169: 378-383.