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Investigating Biosynthetic Steps of an Angucycline Antifungal

From the bacterium Streptomyces sp. SCC-2136 (ATCC 55186), two angucycline natural products are produced, designated Sch 47554 and Sch 47555. These compounds are produced through a type II polyketide biosynthetic pathway. The early biosynthetic steps to these molecules were confirmed. These include the minimal polyketide synthase (PKS), the C-9 ketoreductase, the first-ring aromatase, the subsequent ring cyclase, and two oxy-genases. Also confirmed were the biosynthetic genes responsible for production of the first amicetose moiety, as well as the glycosyltransferase that creates a C-glycosidic bond between the angucyclic scaffold and the amicetose moiety. In confirming these pathways, two new natural products were produced: GG31, an amitosylated rabelomycin, and GG53, rabelomycin hydroxylated at C-12b. Future work will be to understand the late biosynthetic steps and generate new angucyclines through combinatorial biosynthesis.
Date01 January 2016
CreatorsGladstone, S. Gabrielle
Source SetsUtah State University
Detected LanguageEnglish
SourceAll Graduate Theses and Dissertations
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