Molecular Biology Faculty
Mohamed S. Donia
Small-molecule-mediated interactions in complex microbial communities
Much like human beings, microbes often live in diverse communities interacting with both collaborators and competitors. Small molecule natural products mediate a significant portion of these interactions. As expected, the more complex a microbial community is, the richer its small molecule chemical arsenal becomes. This phenomenon has been observed in the complex microbiomes of marine invertebrates, terrestrial soils, human gut, and the plant rhizosphere, among others. Our research interests are mainly to study the chemical and biological interactions within complex microbial communities (microbe-microbe interactions) and between microbial communities and their multicellular hosts (microbe-host interactions). In respect to the human body and its microbial inhabitants (the human microbiome), these interactions can define the difference between commensals and pathogens, and thus between health and disease states. In the case of marine invertebrates (e.g., sponges and ascidians) and their symbionts, these interactions can provide the host with indispensible means of chemical defense, allowing it to survive in a predator-rich environment. In the soil or seawater, these interactions can dictate the microbial community’s composition, fitness and stability over time. Our ongoing efforts towards understanding these interactions will not only explain fundamentals of basic biology in these systems, but will also supply a suite of biologically active small molecules that can be developed as therapeutic agents.
In addition, the Donia lab has a special interest in the uncultivable microbial components of complex communities, which have eluded research attempts for decades despite their abundance and clear importance. Recent advances in the fields of metagenomics and single-cell genomics have allowed access to the genetic information of some of these unculturable microbes, while functional studies remain challenging. Our goal is to develop the necessary computational and experimental tools to functionally study the interactions mediated by uncultivable members of complex microbiomes, using an integrated multi “omics” approach, including metagenomics, metabolomics and metatranscriptomics. The Donia lab functions at the intersection between multiple disciplines: microbiology, molecular biology, biochemistry, small molecule chemistry and biosynthesis, metagenomics and bioinformatics, aiming to answer basic biological questions and to develop new therapeutics.
Donia, M. S.; Cimermancic, P.; Schulze, C. J.; Wieland Brown, L. C.; Martin, J.; Mitreva, M.; Clardy, J.; Linington, R. & Fischbach, M. A. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell. 2014. 158, 6, 1402-1414. Highlighted in Nature, Nature Reviews Microbiology, The New York Times, The Economist, The Huffington Post, Science News, Bioworld, and Biotechniques. PubMed
Williams, B. B.; Van Benschoten, A. H.; Cimermancic, P.; Donia, M. S.; Zimmermann, M.; Taketani, M.; Ishihara, A.; Kashyap, P. C.; Fraser, J. S.; Fischbach, M. A. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host & Microbe. 2014. 16, 1-9. PubMed
Kwan, J. C.; Tianero, M. D.; Donia, M. S.; Wyche, T. P.; Bugni, T.S. & Schmidt, E. W. Host control of symbiont natural product chemistry in cryptic populations of the tunicate Lissoclinum patella. PLoS One. 2014. 5, e95850 PubMed
Marcobal A.; Kashyap P. C.; Nelson T. A.; Aronov P. A.; Donia M. S.; Spormann A.; Fischbach M. A. & Sonnenburg J. L. A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. ISME J. 2013. doi: 10.1038/ismej.2013.89 PubMed
Donia, M. S. & Fischbach M. A. Dyeing to learn more about the gut microbiota. Cell Host Microbe. 2013. 13, 2, 119-120. PubMed
Kwan, J. C.; Donia, M. S.; Han, A. W.; Hirose, E.; Haygood, M. G. & Schmidt, E. W. Genome streamlining and chemical defense in a coral reef symbiosis. Proc. Natl. Acad. Sci. USA. 2012. 109, 50, E20655-60 PubMed
Schmidt, E. W.; Donia, M. S.; McIntosh, J. A.; Fricke, W. F. & Ravel, J. Origin and variation of tunicate secondary metabolites. J. Nat. Prod. 2012. 75, 2, 295-304 PubMed
Tianero, Ma. D.; Donia, M. S.; Young, T. S.; Schultz,P. G.; Schmidt, E. W. Ribosomal route to small molecule diversity. J. Am. Chem. Soc. 2012. 134, 1, 418-425 PubMed
Donia, M. S.; Fricke W. F.; Partensky F.; Cox J.; Elshahawi S. I.; White J. R.; Phillippy A. M.; Schatz M. C.; Piel J.; Haygood M. G.; Ravel J.; Schmidt E. W.; Complex microbiome underlying secondary and primary metabolism in the tunicate-Prochloron symbiosis. Proc. Natl. Acad. Sci. USA. 2011. 108, 51, E1423-1432 PubMed
Highlighted in Nature Biotechnology 30, 1, 2012
McIntosh, J. A., Donia, M. S. & Schmidt, E. W. Enzymatic basis of ribosomal peptide prenylation in cyanobacteria. J. Am. Chem. Soc. 2011, 133, 34, 13698-705. PubMed
Highlighted in Chem. & Eng. News 89, 32, 2011
Donia. M. S.; Ruffner, D. E.; Cao, S.; Schmidt, E. W. Accessing the hidden majority of marine natural products through metagenomics. Chembiochem. 2011. 12, 1230-6 PubMed
Donia, M. S.; Fricke, W. F.; Ravel, J.; Schmidt, E. W. Variation in tropical reef symbiont metagenomes defined by secondary metabolism. PLoS One. 2011. 6, e17897 PubMed
Donia, M. S.; Schmidt, E. W. Linking chemistry and genetics in the growing cyanobactin natural products family. Chem. & Biol. 2011. 18, 508-19. PubMed
Schmidt E. W.; Donia M. S. Life in cellulose houses: symbiotic bacterial biosynthesis of ascidian drugs and drug leads. Curr. Opin. Biotechnol. 2010. 21, 827-833. PubMed
McIntosh, J. A.; Donia, M. S.; Schmidt, E. W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 2010, 132, 12, 4089-91. PubMed
Donia, M. S. & Schmidt, E. W. Cyanobactins – ubiquitous cyanobacterial ribosomal peptide metabolites. in Comprehensive Natural Products II Chemistry and Biology, Vol. 2 539-558 (Elsevier: Oxford, 2010).
Schmidt, E. W.; Donia, M. S. Cyanobactin ribosomally synthesized peptides — a case of deep genome mining. Methods Enzymol. 2009, 458, 575-596. PubMed
McIntosh, J. A.; Donia, M. S.; Schmidt, E. W. Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. Nat. Prod. Rep. 2009, 26, 4, 537-59. PubMed
Donia, M. S.; Ravel, J.; Schmidt, E. W. A global assembly line for cyanobactins. Nature Chem. Biol. 2008, 4, 6, 341-3. PubMed
Donia, M. S.; Hathaway, B. J.; Sudek, S.; Haygood, M. G.; Rosovitz, M. J.; Ravel, J.; Schmidt, E. W. Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nature Chem. Biol. 2006, 2, (12), 729-735. PubMed
Highlighted by Joern Piel in Nature Chem. Biol. 2006, 2, 12, 661-662.