Date of Award:

2016

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Biological and Irrigation Engineering

Advisor/Chair:

Jixun Zhan

Abstract

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.

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