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Vitamin B6 Production in Bacillus subtilis

Interference of Heterologous and Host Pathways

dc.contributor.advisorCommichau, Fabian Moritz Dr.
dc.contributor.authorRosenberg, Jonathan
dc.date.accessioned2018-01-23T10:41:10Z
dc.date.available2018-01-23T10:41:10Z
dc.date.issued2018-01-23
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-002E-E32C-B
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-6683
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-6683
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc570de
dc.titleVitamin B6 Production in Bacillus subtilisde
dc.title.alternativeInterference of Heterologous and Host Pathwaysde
dc.typedoctoralThesisde
dc.contributor.refereeStülke, Jörg Prof. Dr.
dc.date.examination2018-01-11
dc.description.abstractengFermentative production of valuable goods is an economically competitive and ecologically sustainable alternative to chemical synthesis. Several previous studies have been dedicated to the establishment of vitamin B6 production strains, but none was successful to compete with chemical synthesis. Fermentative production of vitamin B6 is hampered by toxic intermediates, a toxic end-product and insufficient knowledge about vitamin B6 homeostasis and related proteins and pathways. This work is dedicated to the identification of deleterious interactions between the heterologous production pathway and the host metabolism, and proposes and applies an approach to design novel, hybrid production pathways combining host underground metabolism and partial heterologous pathways. Mutant derivatives of the Gram-positive model bacterium Bacillus subtilis, which are able to grow in presence of toxic amounts of pyridoxal 5’- phosphate are shown to carry mutations leading to deregulation of the biotin biosynthesis operon. Furthermore, the inhibitor of the threonine synthesis operon ThrR, which is also involved in resistance to the vitamin B6 synthesis intermediate 4-hydroxy-threonine phosphate, is characterized. In order to optimize an existing B6 production strain, targeted evolution is applied leading to a novel, non-native biosynthesis pathway of endogenous underground and heterologous enzyme activities. This approach is regarded to be ubiquitously applicable in different species and for other products and the characterization of the host-heterologous interferences is of great value for future projects for fermentative B6 production.de
dc.contributor.coRefereeLüder, Carsten Prof. Dr.
dc.subject.engVitamin B6de
dc.subject.engFermentationde
dc.subject.engProduction of valuable goodsde
dc.subject.engPyridoxalde
dc.subject.engPyridoxinede
dc.subject.engUnderground Metabolismde
dc.subject.engMetabolic Pathwaysde
dc.subject.engSuppressor Mutantsde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-002E-E32C-B-8
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn1011413795


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