Please use this identifier to cite or link to this item: http://theses.ncl.ac.uk/jspui/handle/10443/5501
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dc.contributor.authorMardiana, Lina-
dc.date.accessioned2022-07-15T10:40:00Z-
dc.date.available2022-07-15T10:40:00Z-
dc.date.issued2021-
dc.identifier.urihttp://hdl.handle.net/10443/5501-
dc.descriptionPhD Thesisen_US
dc.description.abstractThe emergence of antibiotic resistant pathogenic bacteria has created a growing demand for research into new antibiotics. Bacterial natural products, particularly from the genus Streptomyces, have historically provided the basis for many clinically used antibiotics. In this project we have examined a class of natural product polyketides from Streptomyces as potential new mode of action antibiotics. We have focussed our investigation on two polyketides, (-)-rishirilide A and (+)-rishirilide B, originally isolated from Streptomyces rishiriensis OFR-1056. Following optimisation of fermentation and isolation protocols, milligram quantities of both (-)-rishirilide A and (+)- rishirilide B were obtained from Streptomyces albus::cos4. (-)-Rishirilide A displays antibiotic activity against Gram-positive bacteria (MICs: S. aureus, 1.56 µg/mL; B. subtilis, 3.125 µg/mL). Mode of action investigations showed that treatment with (-)-rishirilide A results in the depolarization of the bacterial cell membrane (B. subtilis 168CA). This may be due to (-)- rishirilide A acting as an irreversible inhibitor through Michael addition with a thiol containing enzyme. Further work will involve the synthesis of chemical probes based on (-)-rishirilide A to identify target enzymes. Additionally, we have supported this work with a study into the high-throughput nanoscale crystallisation (ENaCt) of natural products for single crystal X-ray analysis. Using ENaCt we have examined the crystallisation of a range of natural products. Cannabidiol and rifampicin crystals were obtained, and single crystal X-ray diffraction analysis successfully performed.en_US
dc.description.sponsorshipIndonesian Endowment Fund (LPDP)en_US
dc.language.isoenen_US
dc.publisherNewcastle Universityen_US
dc.titleInvestigation of the production, isolation and bioactivity of the rishirilide natural products including crystallographic studiesen_US
dc.typeThesisen_US
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