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A Multifaceted Approach to Improve Upon the Freshwater Cyanobacteria Drug Lead Discovery Pipeline
Author(s) -
Sullivan Peter,
May Daniel,
Crnkovic Camila,
Orjala Jimmy
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.818.5
Subject(s) - cyanobacteria , drug discovery , biochemical engineering , bioassay , computational biology , isolation (microbiology) , workflow , biology , drug , pipeline (software) , microbiology and biotechnology , bacteria , computer science , bioinformatics , ecology , engineering , pharmacology , genetics , database , programming language
Natural products have long been an excellent drug lead source. Our drug discovery workflow has resulted in the isolation of many cyanobacterial compounds active in a wide range of antibacterial, antiviral, and anticancer bioassays. While the present bioassay‐guided drug lead discovery has proven successful, we are currently developing a multifaceted strategy to improve upon this process in order to maximize the isolation and elucidation of novel, active cyanobacterial secondary metabolites. The first aspect to this approach is to expand our strain collection process by isolating cyanobacteria directly from the soil. Utilizing a pair of cyanobacterial specific 16S rRNA primers we have been able to identify cyanobacteria in the soil without macroscopic growth. Then, using inorganic media and light, we are able to culture the cyanobacteria directly from the soil for addition into our strain library. In addition, we are in the process of optimizing the culture media in order to maximize production of metabolites of interest. Using a comparative metabolomics approach, we were able to assess the influence of media components on the overall metabolic profile of cyanobacterial strains, assisting in the selection of best culture conditions for the purpose of drug discovery. The third feature to modifying our drug discovery pipeline is the incorporation of phylogenetics. Because metabolic production has shown to correlate with taxonomy, we can systematically prioritize which strains to culture and ultimately test against a particular bioassay. Overall, these measures have the capacity to significantly improve our lab's drug lead output. Support or Funding Information NIH/NCI ‐ Grant PO1CA125066‐07 NIH NCCIH ‐ Grant T32AT007533 Science without Borders ‐ 13055‐13‐5