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dc.contributor.advisorGregory Stephanopoulos.en_US
dc.contributor.authorChatzivasileiou, Alkiviadis Orfefs.en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemical Engineering.en_US
dc.date.accessioned2019-12-13T18:57:19Z
dc.date.available2019-12-13T18:57:19Z
dc.date.copyright2019en_US
dc.date.issued2019en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/123243
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2019en_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractIsoprenoids comprise a large class of chemicals, of significant interest due to their diverse properties. Most isoprenoids are plant secondary metabolites and are of commercial importance due to their varied applications in fields spanning medicine, agriculture, flavors, fragrances, cosmetics and nutrition. Biological production of isoprenoids in microbes is considered to be the most efficient and commercially viable way for their large-scale production. Thus far, isoprenoid biosynthesis has been performed through pathways inextricably linked to glycolysis. Furthermore, these pathways are inherently limited due to their extensive cofactor requirements, complex regulation and large number of steps. In this thesis we present a novel pathway for isoprenoid synthesis, the Isopentenol Utilization Pathway (IUP), which aims to overcome these limitations.en_US
dc.description.abstractThis pathway functions through the double phosphorylation of an isopentenol, either isoprenol or prenol, to produce the main precursors to isoprenoid synthesis, isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP). This pathway is radically different from naturally-occurring pathways or their engineered variants because it is only two steps long, uses an externally-provided isoprenol as its substrate instead of a glucose-derived catabolite, and uses only a single co-factor, ATP. We identify suitable enzymes, construct the pathway and proceed to demonstrate an in vivo proof of concept. After optimizing the pathway feedstock, we proceed to show that IUP is decoupled from central carbon metabolism. We demonstrate that the IUP can quickly produce copious amounts of IPP & DMAPP and can be used for the production of a variety of isoprenoids.en_US
dc.description.abstractThe IUP flux exceeded the capacity of almost all downstream pathways tested, was competitive with the highest isoprenoid fluxes reported as well as against state-of-the art isoprenoid pathways. Furthermore, we elaborate on our progress towards improving the capacity of a downstream farnesene synthesis pathway, to catch up with and fully utilize IUP's production capacity. Finally, we propose a new scheme for the use of the IUP to produce functionalized isoprenoids using functionalized isopentenols to introduce functionalizations in isoprenoid backbones, and we show preliminary results of this application.en_US
dc.description.statementofresponsibilityby Alkiviadis Orfefs Chatzivasileiou.en_US
dc.format.extent215 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemical Engineering.en_US
dc.titleEngineering a novel pathway for isoprenoid synthesisen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.identifier.oclc1130059461en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Chemical Engineeringen_US
dspace.imported2019-12-13T18:57:18Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentChemEngen_US


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