Bioproduction of L-tyrosine and L-tyrosine derivatives by biosensing and modular co-culture engineering approaches
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Li, Zhenghong.
Bioproduction of L-tyrosine and L-tyrosine derivatives by biosensing and modular co-culture engineering approaches. Retrieved from
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TitleBioproduction of L-tyrosine and L-tyrosine derivatives by biosensing and modular co-culture engineering approaches
Date Created2020
Other Date2020-05 (degree)
Extent1 online resource (xiii, 157 pages) : illustrations
DescriptionProducing 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.
NotePh.D.
NoteIncludes bibliographical references
Genretheses, ETD doctoral
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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