Date of Award:
Master of Science (MS)
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 keteoreductase, the first-ring aromatase, the subsequent ring cyclase, and two oxygenases. 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 patways, two new natural products were produced: GG31, an amitosylated rabelmycin, and GG53, rabelmycin hydroxylated at C-12b. Future work will be to understand the late biosynthetic steps and generate new angucyclines through combinatorial biosynthesis.
Gladstone, S. Gabrielle, "Investigating Biosynthetic Steps of an Angucycline Antifungal" (2016). All Graduate Theses and Dissertations. 4952.
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