Date of Award:

5-2016

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Biological Engineering

Committee Chair(s)

Jixun Zhan

Committee

Jixun Zhan

Committee

Ron Sims

Committee

Anhong Zhou

Abstract

The species of bacterium Streptomyces sp. SCC-2136 which has the American Type Culture Collection index 55186 naturally produces two chemical compounds, labeled Sch 47554 and Sch 47555. These compounds were previously reported to posess antifungal activity. This thesis sets out to confirm the mechanism by which the bacterium produces these compounds; specifically which genes are responsible for producing the enzymes that make and shape the molecules.

The genes and enzymes that were characterized are the minimal polyketide synthase, the ketoreductase that specifically acts on the ninth carbon, the first-ring aromatase, the subsequent ring cyclase, and two oxygenases. Also elucidated were the genes responsible for production of the first sugar (called amicetose) in the chain of two sugars attached to carbon 9 as well as the glycosyltransferase enzyme that attaches this sugar to the rest of the molecule.

In confirming these pathways, two new compounds were produced: GG31, which has a base structure of the antibiotic rabelomycin but is attached at carbon 9 to a molecule of the deoxysugar amicetose; and GG53 which has the base structure of rabelomycin but with a hydroxyl group at carbon 12b. Future work will be to understand the later biosynthetic steps and generate new related molecules through combinatorial biosynthesis.

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