Show simple item record

dc.contributor.authorMacLeod, Jeanna
dc.date.accessioned2017-12-05T17:11:54Z
dc.date.available2017-12-05T17:11:54Z
dc.identifier.urihttp://hdl.handle.net/10222/73461
dc.description.abstractNatural product biosynthesis in Streptomyces venezuelae ISP5230 was investigated in three ways. First, through precursor-directed jadomycin biosynthesis using non-proteinogenic amino acids (4-(aminomethyl)benzoic acid, 3-(aminomethyl)benzoic acid, 8-aminooctanoic acid), five novel jadomycins were isolated and characterized. Four novel jadomycins were evaluated for cytotoxic activity in drug-sensitive and drug-resistant cancer cells and a panel of six microbes. Next, jadomycin C-glycoside production was attempted by heterologous expression of urdGT2 in place of the native O-glycosyltransferase, jadS. C-glycoside production was not observed from three complementation methods pursued. Finally, a S. venezuelae mutant was prepared to evaluate a silent biosynthetic gene cluster identified through genome mining. While the changes to the biosynthetic profile were apparent in the activator overexpression mutant, the major products detected were previously identified metabolites of tryptophan, including tryptophol. The studies demonstrated the pliability of S. venezuelae ISP5230 as a producer of natural products through manipulations to growth conditions, supplementation, and genetic variation.en_US
dc.language.isoenen_US
dc.subjectNatural productsen_US
dc.subjectJadomycinsen_US
dc.subjectStreptomyces venezuelaeen_US
dc.subjectPolyketide biosynthesisen_US
dc.titleNatural Product Biosynthesis by Streptomyces venezuelae: Genetic Variants for Drug Discoveryen_US
dc.date.defence2017-11-08
dc.contributor.departmentCollege of Pharmacyen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinern/aen_US
dc.contributor.graduate-coordinatorDr. David L. Jakemanen_US
dc.contributor.thesis-readerDr. Kerry B. Goralskien_US
dc.contributor.thesis-readerDr. Tannis Jurgensen_US
dc.contributor.thesis-supervisorDr. David L. Jakemanen_US
dc.contributor.ethics-approvalNot Applicableen_US
dc.contributor.manuscriptsYesen_US
dc.contributor.copyright-releaseNot Applicableen_US
 Find Full text

Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record