The incidence of fungal infection has been steadily increasing among immunosuppressed and cancer patients. For this reason, there is a need for an effective, non-toxic water soluble antifungal agent. The objective is to prepare and characterize the novel antifungal antibiotic hydroheptin, which is a member of the non-aromatic heptaene macrolide group and is reported to be water soluble. The specific aims in Phase I will be: (1) Evaluation of various cultures and characterization of the best hydroheptin producers, (2) Development of analytical HPLC assay method for quantitation, (3) Development of fermentation conditions, (4) Scale-up of the fermentation to Pilot scale, (5) Development of an efficient isolation/purification method, and (6) Preparation of sufficient material for biological and physicochemical studies. Strain improvement, structural characterization, chemical modifications and extended antifungal activity evaluation will be performed in Phase II. Information, that unparts water solubility to hydroheptin, may be translated into other polyene macrolides for improvement of water solubility and antifungal activity.Awardee's statement of the potential commercial applications of the research:Hydroheptin has been reported to be water-soluble and relatively stable. Thus, the elucidation of the molecular structure of hydroheptin and subsequent optimization of biological activity could result in an effective antifungal compound with minimal or no toxicity. We will develop this antifungal agent on a large scale for clinical applications.National Cancer Institute (NCI)
