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Optimization of the Production and Isolation of the Novel Antifungal Occidiofungin

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI122441-01A1
Agency Tracking Number: R41AI122441
Amount: $529,551.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA15-270
Timeline
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-03-15
Award End Date (Contract End Date): 2018-06-30
Small Business Information
606 COACHLIGHT CT
College Station, TX 77845-8145
United States
DUNS: 078514829
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 JAMES SMITH
 (979) 703-1517
 jsmith@bio.tamu.edu
Business Contact
 JAMES SMITH
Phone: (979) 845-2417
Email: james.smith@sanochemicals.com
Research Institution
 TEXAS A&M UNIVERSITY
 
400 HARVEY MITCHELL PARKWAY SOUTH
COLLEGE STATION, TX 77845-4375
United States

 Nonprofit college or university
Abstract

DESCRIPTION provided by applicant Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar fungicidal activity against a broad spectrum of fungi Occidiofungin is produced by the Gram negative bacterium Burkholderia contaminans From our structural characterization studies occidiofungin was determined to have a unique chemical composition Our studies have also revealed that occidiofungin has a novel mechanism of action Occidiofungin is a potent antifungal against fluconazole and caspofungin resistant Candida albicans Occidiofungin triggers cell death by inducing apoptosis in yeast cells Occidiofungin has minimal toxicity in mice at doses exceeding mg kg Furthermore occidiofungin was shown to reduce Candida glabrata load in the kidneys of infected mice All these studies point to the need to further the preclinical development of this novel compound The major impediment to furthering investigational studies on this unique antifungal compound is the poor yield from culture liquor The goal of this application is to enhance the yield and purity of occidiofungin following fermentation Three approaches will be explored to increase the yield of the antifungal compound First media components will be screened to determine their effect on the production levels of the antifungal compound Second a molecular based approach will be used to determine whether an increase in production of occidiofungin is possible through genetic manipulation of B contaminans Our third approach is to develop a heterologous expression system The last component of the application is to determine the most effective means of extracting and purifying the antifungal compound from the fermentation liquor These studies will enable exploratory structure activity relationship SAR studies on occidiofungin This work is necessary for furthering additional studies aimed at developing the antifungal compound as a new therapeutic PUBLIC HEALTH RELEVANCE The proposal addresses the need for the development of a novel broad spectrum antifungal for the treatment of systemic fungal infections We will investigate means of enhancing the production and purification of an antifungal compound named occidiofungin This work is necessary for promoting the production of sufficient amounts of occidiofungin for the completion of the required preclinical studies that are needed for filing n Investigational New Drug IND application

* Information listed above is at the time of submission. *

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