Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent, as an example.
Analysis of the genome of Streptomyces aizunensis NRRL B-11277 indicated its potential to produce a compound of novel and highly predictable structure. The structure was predicted with sufficient accuracy to allow straightforward detection of the specific metabolite in HPLC profiles of fermentation extracts and hence to guide the isolation. The spectroscopic work was reduced to a confirmation of structure rather than a first principle determination. The compound, ECO-02301 (1), demonstrated potent antifungal activity. This work exemplifies not only the discovery of novel antibiotics from well-characterized organisms but also the utility of genomics as a further tool, complementary to spectroscopy, to enable rapid determination of complex structures.
McAlpine
James B
JB
Ecopia BioSciences, Inc., 7290 Frederick Banting Street, Montréal, Québec, H4S 2A1, Canada. mcalpine@ecopiabio.com
Bachmann
Brian O
BO
Piraee
Mahmood
M
Tremblay
Steve
S
Alarco
Anne-Marie
AM
Zazopoulos
Emmanuel
E
Farnet
Chris M
CM
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D023281:Genomics; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011090:Polyenes / Q000737:chemistry / Q000494:pharmacology*; D013302:Streptomyces / Q000235:genetics*
D000935:Antifungal Agents; C501021:ECO-02301; D011090:Polyenes