- Ph.D. University of Ottawa, Canada
- Assistant Professor of Pharmacognosy
- Assistant Research Professor in the Research Institute of Pharmaceutical Sciences
Our research questions and explores the utility provided by specialized metabolites to the producing organism. What do natural products do? The simplicity about this question belies its complexity. While the therapeutic activities of bacterial natural products have driven broad, activity-based discovery efforts, the benefits that the majority of secondary metabolites provide to producing bacteria have been obfuscated by their clinical applications and successes. Investigating the predatory capabilities of myxobacteria, we seek to determine the exchange of specialized metabolites amongst microbes during predation. Developing predator-prey pairings with ecologically relevant prey, we hope to learn how myxobacteria have evolved to combat bacterial behaviors pertinent to clinical concerns such as biofilm formation and persistence.
Myxobacteria as perceptive predators
Quorum signaling amongst microbes is amazing. However the impact of these quorum signals, often produced at relatively high quantities necessary to facilitate cell-cell communication, on neighboring unrelated microbes throughout highly diverse environments remains underexplored. The observation that the myxobacterium Myxococcus xanthus senses and responds to quorum signals produced by its prey (Whitworth Group; Aberystwyth University) provides an excellent example of functional interspecies signaling. Our group is currently investigating the breadth of chemical signals recognized by myxobacteria and how this predatory eavesdropping might impact the production of antimicrobial metabolites. (NIAID: R15AI137996)
Heterologous production of metabolites from myxobacteria
When a natural product from myxobacteria demonstrates intriguing activity but can only be isolated at exceedingly low quantities, heterologous expression of the associated biosynthetic pathway might provide better access to the active metabolite. Currently, we are developing heterologous platforms to produce the eukaryotic translation factor inhibitor, gephyronic acid. The natural producing organism produces a mere 3mg/L of gephyronic acid, and these alternative platforms would provide better access and facilitate downstream assessment of this promising anticancer drug candidate. (NCI: R03CA219320)
- Adaikpoh B.I., Akbar S., Albataineh H., Misra S.K., Sharp J..S, Stevens D.C. Myxobacterial Response to Methyljasmonate Exposure Indicates Contribution to Plant Recruitment of Micropredators. Front. in Microbiol. 2020, doi: 10.3389/fmicb.2020.00034
- Albataineh H., Duke M., Misra S.K., Sharp J.S., Stevens D.C. Solo acylhomoserine lactone synthase from predatory myxobacterium suggests beneficial participation in interspecies cross talk. bioRxiv. 2019, https://doi.org/10.1101/849075
- Gregory K., Salvador L.A., Akbar S., Adaikpoh B.I., Stevens D.C. Survey of Biosynthetic Gene Clusters from Sequenced Myxobacteria Reveals Unexplored Biosynthetic Potential. Microorganisms 2019, 7, 181.
- Granatosky E.A., DiPrimio N., Pickering J.R.E., Stevens D.C., Perlstein E.O., Taylor R.E. GEX1A, a Polyketide from Streptomyces chromofuscus, Corrects the Cellular Defects Associated with Niemann-Pick Type C1 in Human Fibroblasts. J. Nat Prod. 2018; 81(9):2018-2025.
- Albataineh H., Stevens D.C. Marine Myxobacteria: A Few Good Halophiles. Marine Drugs. 2018; 16(6).
- Wagner D.T.*, Stevens D.C.*, Mehaffey M.R., Taylor R.E., Brodbelt J.S., & Keatinge-Clay A.T. 2016 α-Methylation follows condensation in the gephyronic acid modular polyketide synthase. Chem Commun (Camb). 52(57), 8822-5. *Co-first authors
- Young J., Stevens D.C., Carmichael R., Tan J., Rachid S., Boddy C.N., Müller R., & Taylor R.E. 2013 Elucidation of Gephyronic Acid Biosynthetic Pathway Revealed Unexpected SAM Dependent Methylations. J. Nat. Prod. 76(12), 2269-76.
- Stevens D.C., Hari T.P.A. & Boddy C.N. 2013 The role of transcription in heterologous expression of polyketides in bacterial hosts. Nat. Prod. Rep. 30, 1391-1411.
- Stevens D.C., Conway K., Pearce N., Villegas-Peñaranda L.R., Garza A., & Boddy C.N. 2013 Alternative sigma factor over-expression enables heterologous expression of a type II polyketide biosynthetic pathway in Escherichia coli. PLoS ONE 8: e64858.