Vitamin B6 Production in Bacillus subtilis

Rosenberg, Jonathan

Interference of Heterologous and Host Pathways

dc.contributor.advisor	Commichau, Fabian Moritz Dr.
dc.contributor.author	Rosenberg, Jonathan
dc.date.accessioned	2018-01-23T10:41:10Z
dc.date.available	2018-01-23T10:41:10Z
dc.date.issued	2018-01-23
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-002E-E32C-B
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-6683
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-6683
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570	de
dc.title	Vitamin B6 Production in Bacillus subtilis	de
dc.title.alternative	Interference of Heterologous and Host Pathways	de
dc.type	doctoralThesis	de
dc.contributor.referee	Stülke, Jörg Prof. Dr.
dc.date.examination	2018-01-11
dc.description.abstracteng	Fermentative 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.coReferee	Lüder, Carsten Prof. Dr.
dc.subject.eng	Vitamin B6	de
dc.subject.eng	Fermentation	de
dc.subject.eng	Production of valuable goods	de
dc.subject.eng	Pyridoxal	de
dc.subject.eng	Pyridoxine	de
dc.subject.eng	Underground Metabolism	de
dc.subject.eng	Metabolic Pathways	de
dc.subject.eng	Suppressor Mutants	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-002E-E32C-B-8
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.identifier.ppn	1011413795

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1213]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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