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Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes
Thesis (PhD)--Stellenbosch University, 2017.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2017
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| _version_ | 1867613953752825856 |
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| access_status_str | Open Access |
| author | Muneri, Ndivhuwo Olga |
| author2 | Strauss, Erick |
| author_browse | Muneri, Ndivhuwo Olga Strauss, Erick |
| author_facet | Strauss, Erick Muneri, Ndivhuwo Olga |
| author_sort | Muneri, Ndivhuwo Olga |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2017. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/101466 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:44:20.637Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/101466 Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes Muneri, Ndivhuwo Olga Strauss, Erick Moracci, Marco Stellenbosch University. Faculty of Science. Dept. of Biochemistry. Glycosidase derived biocatalysts Thioglycoligase Mycothiol pathway enzymes UCTD Thesis (PhD)--Stellenbosch University, 2017. ENGLISH ABSTRACT: Glycosides are complex carbohydrates that are involved in essential cellular and molecular biological processes within all living organisms. In addition, certain glycosides have anti-cancer, antioxidant, anti-inflammatory, antibacterial, antiviral, antiparasitic and antifungal activities. The functions of glycosides in biological processes and in biomedicine have led to a high demand for these organic molecules. However, the study of glycosides is hindered by the practical challenges in generating these compounds synthetically. This is even more true in the case of glycosides bound by means of α-glycosidic bonds, as most of the available synthetic methods promote the formation of β-glycosides. Methods that form α-glycosides are either low yielding or also promotes β-glycoside formation, resulting in the formation of mixtures that are challenging to separate. During the course of this study novel α- thioglycoligases derived from a CAZy family GH89 α-N-acetylglucosaminidase were prepared and characterized for their ability to form α-glycosides through biotransformation. The utility of the new biocatalysts was showcased by preparing several α-GlcNAc-based glycosides of biomedical and chemical interest. The products were purified or modified further through chemical transformations (such as “Click”-cycloaddition) and subsequently tested as potential small molecules chaperones for the treatment of Sanfilippo syndrome and/or as alternative substrates for the MshB, a mycothiol biosynthetic enzyme that has been identified as a potential target for development of new antituberculosis agents. Through the discovery of these molecules and the development of a new continuous deacetylase enzyme assay the findings of this study will significantly strengthen our ability to mobilise α-GlcNAc-based glycosides as part of ongoing research efforts in these fields. AFRIKAANSE OPSOMMING: Glikosiede is komplekse koolhidrate wat betrokke is by noodsaaklike sellulêre en molekulêre biologiese prosesse binne alle lewende organismes. Daarbenewens het sommige glikosiede ook anti-kanker, anti-oksidant, anti-inflammatoriese, antibakteriële, antivirale, antiparasitiese en antifungale aktiwiteite. Die funksies van glikosiede in biologiese prosesse en in die biomediese vakgebied het gelei tot 'n groot aanvraag vir hierdie organiese molekules. Die studie van glikosiede word egter verhinder deur die praktiese uitdagings om hierdie verbindings sinteties te berei. Dit is selfs meer waar in die geval van glikosiede gebind deur middel van α-glikosidiese bindings, aangesien die meeste van die beskikbare sintetiese metodes die vorming van β-glikosiede bevorder. Metodes wat α-glikosiede vorm het óf 'n lae opbrengs óf bevorder ook β-glikosied-vorming, wat lei tot die vorming van mengsels wat uitdagend is om te skei. Gedurende die verloop van hierdie studie is nuwe α- tioglikoligases wat afgelei is van 'n CAZy familie GH89 α-N-acetylglucosaminidase berei en gekarakteriseer vir hul vermoë om α-glikosiede vorm deur biotransformasie. Die nut van die nuwe biokataliste is ten toon gestel deur die voorbereiding verskeie α-GlcNAc-gebaseerde glikosiede van biomediese en chemiese belang. Die produkte is gesuiwer of verder verander deur chemiese transformasies (soos "Click"-sikloaddisie reaksies) en daarna getoets as potensiële klein molekule chaperones vir die behandeling van Sanfilippo sindroom en/of as alternatiewe substrate vir MshB, 'n mikotiol biosintetiese ensiem wat geïdentifiseer is as 'n potensiële teiken vir die ontwikkeling van nuwe antituberkulose middels. Deur die ontdekking van hierdie molekules en die ontwikkeling van 'n nuwe deurlopende deasetieleringsensiem-essaï sal die bevindinge van hierdie studie ons vermoë om α-GlcNAc-gebaseerde glikosiede te mobiliseer as deel van volgehoue navorsing op hierdie gebied aansienlik versterk. Doctoral 2017-02-22T09:29:47Z 2017-03-29T21:04:09Z 2018-12-31T03:00:13Z 2017-03 Thesis http://hdl.handle.net/10019.1/101466 en_ZA Stellenbosch University 187 pages : illustrations application/pdf application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Glycosidase derived biocatalysts Thioglycoligase Mycothiol pathway enzymes UCTD Muneri, Ndivhuwo Olga Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| title | Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| title_full | Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| title_fullStr | Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| title_full_unstemmed | Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| title_short | Engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| title_sort | engineering and application of glycosidase derived biocatalysts in the study of mycothiol pathway enzymes |
| topic | Glycosidase derived biocatalysts Thioglycoligase Mycothiol pathway enzymes UCTD |
| url | http://hdl.handle.net/10019.1/101466 |
| work_keys_str_mv | AT munerindivhuwoolga engineeringandapplicationofglycosidasederivedbiocatalystsinthestudyofmycothiolpathwayenzymes |