001047604 001__ 1047604
001047604 005__ 20260220104403.0
001047604 020__ $$a978-3-95806-862-9
001047604 037__ $$aFZJ-2025-04406
001047604 1001_ $$0P:(DE-Juel1)188446$$aHaase, Mona$$b0$$eCorresponding author$$ufzj
001047604 245__ $$aApplication of C3-methyltransferases for natural product synthesis$$f - 2025-09-08
001047604 260__ $$aJülich$$bForschungszentrum Jülich GmbH Zentralbibliothek, Verlag$$c2025
001047604 300__ $$a432
001047604 3367_ $$2DataCite$$aOutput Types/Dissertation
001047604 3367_ $$0PUB:(DE-HGF)3$$2PUB:(DE-HGF)$$aBook$$mbook
001047604 3367_ $$2ORCID$$aDISSERTATION
001047604 3367_ $$2BibTeX$$aPHDTHESIS
001047604 3367_ $$02$$2EndNote$$aThesis
001047604 3367_ $$0PUB:(DE-HGF)11$$2PUB:(DE-HGF)$$aDissertation / PhD Thesis$$bphd$$mphd$$s1768388750_12505
001047604 3367_ $$2DRIVER$$adoctoralThesis
001047604 4900_ $$aBioorganische Chemie an der Heinrich-Heine-Universität im Forschungszentrum Jülich$$v52
001047604 502__ $$aDissertation, Düsseldorf, 2025$$bDissertation$$cDüsseldorf$$d2025
001047604 520__ $$aNatural products play a vital role in drug development, either directly as pharmaceuticals or as templates for designing target-specific therapeutics. The chemical synthesis of these compounds often presents significant challenges, requiring multiple reaction steps and hazardous reagents. One prominent structural motif found in numerous bioactive natural products is the hexahydropyrrolo[2,3- b]indole (HPI) framework. Its unique tricyclic structure and diverse biological activities have driven significant synthetic interest, yet traditional methods struggle to achieve stereoselectivity efficiently. This thesis aims to develop a biocatalytic route for synthesising the HPI motif using methyltransferases (MTases), which catalyses C3-methylation of tryptophan-based cyclic dipeptides (DKPs). The MTase StspM1 from Streptomyces sp. HPH0547 was selected as the starting point for these studies: Optimised reaction conditions, enzyme immobilisation, and S-adenosyl methionine (SAM) cofactor recycling were investigated to create a scalable, efficient method. To broaden the understanding of their catalytic functions, homologs of StspM1 were explored, focusing on their structure and mechanism. This investigation was supported by two crystal structures obtained during the study. Computational docking and mutagenesis confirmed key residues critical for activity. Among these homologs, SgMT from Streptomyces griseoviridis was successfully integrated into the total synthesis of the natural product lansai B, demonstrating its synthetic utility. The gene clusters linked to these C3-MTases involve additional enzymes contributing to the biosynthesis of lansai B, including a second MTase, a cyclodipeptide synthase (CDPS) and a prenyltransferase (PTase). The second MTase was confirmed to function as an N-MTase. The PTase was found to prenylate the C5-position, representing the final step in the biosynthesis of lansai B This work advances biocatalytic strategies for synthesising complex natural product frameworks, offering new methodologies for pharmaceutical development.
001047604 536__ $$0G:(DE-HGF)POF4-2172$$a2172 - Utilization of renewable carbon and energy sources and engineering of ecosystem functions (POF4-217)$$cPOF4-217$$fPOF IV$$x0
001047604 909CO $$ooai:juser.fz-juelich.de:1047604$$pVDB
001047604 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)188446$$aForschungszentrum Jülich$$b0$$kFZJ
001047604 9101_ $$0I:(DE-HGF)0$$6P:(DE-Juel1)188446$$a HHU Düsseldorf$$b0
001047604 9131_ $$0G:(DE-HGF)POF4-217$$1G:(DE-HGF)POF4-210$$2G:(DE-HGF)POF4-200$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-2172$$aDE-HGF$$bForschungsbereich Erde und Umwelt$$lErde im Wandel – Unsere Zukunft nachhaltig gestalten$$vFür eine nachhaltige Bio-Ökonomie – von Ressourcen zu Produkten$$x0
001047604 9141_ $$y2025
001047604 920__ $$lyes
001047604 9201_ $$0I:(DE-Juel1)IBOC-20090406$$kIBOC$$lInstitut für Bioorganische Chemie (HHUD)$$x0
001047604 980__ $$aphd
001047604 980__ $$aVDB
001047604 980__ $$abook
001047604 980__ $$aI:(DE-Juel1)IBOC-20090406
001047604 980__ $$aUNRESTRICTED