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Bioproduction of L-tyrosine and L-tyrosine derivatives by biosensing and modular co-culture engineering approaches
Descriptive
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Title
Bioproduction of L-tyrosine and L-tyrosine derivatives by biosensing and modular co-culture engineering approaches
Name
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Li
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Zhenghong
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Zhenghong Li
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author
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Zhang
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Haoran
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Haoran Zhang
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Advisory Committee
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chair
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Pedersen
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Henrik
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Henrik Pedersen
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Advisory Committee
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internal member
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Schuster
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Benjamin
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Benjamin Schuster
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Advisory Committee
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internal member
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Wang
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Lu
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Lu Wang
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Advisory Committee
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(authority = RULIB)
outside member
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Rutgers University
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degree grantor
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School of Graduate Studies
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theses
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2020
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2020-05
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2020
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English
Abstract
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Producing aromatic compounds, especially by using sustainable and environmentally friendly methods, is of great research and application significances. L-Tyrosine is one of 20 standard amino acids and is a key precursor for biosynthesis of a wide range of valuable biochemicals. This thesis research focuses on constructing a microbial L-tyrosine producer and utilizing it as a versatile platform for bioproduction of value-added L-tyrosine derivatives. For developing a L-tyrosine overproducer, key L-tyrosine biosynthesis pathway enzymes were first over-expressed in E. coli. Subsequently, a biosensor-assisted cell selection system was established which, via utilization of a tyrosine biosensor protein TyrR, maintained the growth of high performing cells in an isogenic population and repressed the growth of the low performing cells. The experimental results showed that this method resulted in a 5.9-fold improvement of L-tyrosine production. On the other hand, overproduction of tyrosine derivatives, including phenol, 4-hydroxystyrene, caffeic acid and rosmarinic acid, were also investigated. Specifically, modular co-culture engineering approaches were utilized for high-efficiency biosynthesis of these products. The biosynthetic pathways for these products were divided into separate modules, each of which was contained in one specialized E. coli strain. By using this approach, phenol, 4-hydroxystyrene, caffeic acid, and rosmarinic acid production was improved for 5.3, 2.5, 1.2, and 38 folds, respectively. Moreover, selected biosensors were used in a growth regulation strategy in co-culture system, which was designed to automatically adjust the cell growth behavior based on the tyrosine availability change. For 4-hydroxystyrene and caffeic acid, the integrated use of biosensors and modular co-culture engineering resulted in 2.7 folds and 2.5 folds production enhancement for 4-hydroxystrene and caffeic acid, respectively, compared with co-culture systems without biosensor, and 6.9 folds and 2.9 folds improvement compared with the monoculture controls. The accomplishments of this thesis study demonstrate that biosensing and modular co-culture engineering are valuable tools for future development of metabolic engineer and microbial biosynthesis.
Subject
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Topic
Biosensors
Subject
(authority = LCSH)
Topic
Tyrosine
Subject
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Topic
Chemical and Biochemical Engineering
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Rutgers University Electronic Theses and Dissertations
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ETD_10892
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1 online resource (xiii, 157 pages) : illustrations
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Ph.D.
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Includes bibliographical references
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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doi:10.7282/t3-hqne-vs59
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ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
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Li
GivenName
Zhenghong
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Permission or license
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2020-04-29 23:23:49
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Zhenghong Li
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Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2020-05-31
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2020-11-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2020-05-04T13:36:14
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2020-05-04T13:36:14
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