ERYTHROMYCIN ANALOGS BY METABOLIC ENGINEERING

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DESCRIPTION (Adapted from the application): Novel molecular genetic methods are now being used to generate antibiotic structures that could not be cost-effectively produced through chemical synthesis. The new methods of "combinatorial biosynthesis" and molecular biological "metabolic engineering" use the special tools of Actinomycete molecular genetics and the growing collection of cloned and sequenced antibiotic biosynthetic pathway genes. Already, many structures have been created and at least one tailored structure 6-deoxyerythromycin, has been produced with improved properties over the parent compound. The applicant proposes to expand the potential number of new structures that can be created through the development of new gene transfer systems in organisms that make other 14-member ring macrolide antibiotics similar to erythromycin. They propose to clone new homologs of existing "tailoring" enzymes and inactivate them to generate new structures with improved chemical or biological activity that could lead to the development of new chemical intermediates and possibly new antibiotics. PROPOSED COMMERCIAL APPLICATION: We are proposing to create novel analogs of 14-membered macrolide antibiotics with potential therapeutic value that will be useful as new chemical intermediates or new human or veterinary therapeutics. The market for macrolide antibiotics is in the hundreds of millions of dollars per year and is still growing. The commercial potential for our new structures is significant.