Metabolic engineering for the production of polylactic acid (PLA) and its copolymers = 폴리유산과 그의 공중합체의 생산을 위한 대사공학적 연구

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Polylactic acid (PLA) is a promising biomass-derived polymer that possesses material properties suitable for household products, commercial plastics, and biomedical materials. However, PLA is currently synthesized by a two-step process: fermentative production of lactic acid followed by complicated chemical polymerization. In this study, $\It{Escherichia coli}$ strains have been developed for one-step production of PLA homopolymer and its various copolymers composed of lactate and hydroxyalkanoates monomers. $\It{E. coli}$metabolism was rationally modified by systems-level metabolic engineering based on $\It{in silico}$ genome-scale metabolic flux analysis to reduce by-products formation, increase the metabolic flux towards lactyl-CoA, and ultimately to enhance biosynthesis of PLA polymers. For more efficient production of PLA polymers, the metabolic pathways were reengineered so that induction with an expensive inducer for the gene expression and feeding of dicarboxylic acid for the cell growth could be avoided. Also, type II PHA synthases from various $\It{Pseudomonas}$ strains were engineered for the production of PLA polymers, which allowed diversification of natural variants of lactate-polymerizing enzyme. Furthermore, various PLA copolymers including poly(lactate-$\It{co}$-glycolate) could be produced by further metabolic engineering. Thus, the strategy of combined metabolic engineering and enzyme engineering allowed efficient bio-based one-step production of PLA and its copolymers. This strategy should be generally useful for developing other engineered organisms capable of producing various unnatural polymers by direct fermentation from renewable resources.
Advisors
Lee, Sang-Yupresearcher이상엽researcher
Description
한국과학기술원 : 생명화학공학과,
Publisher
한국과학기술원
Issue Date
2010
Identifier
418815/325007  / 020065155
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2010.2, [ ii, 146 p. ]

Keywords

Polylactic acid; E. coli; Enzyme engineering; Metabolic engineering; Polyhydroxyalkanoate; 폴리하이드록시알카노에이트; 폴리유산; 대장균; 효소공학; 대사공학

URI
http://hdl.handle.net/10203/29087
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=418815&flag=dissertation
Appears in Collection
CBE-Theses_Ph.D.(박사논문)
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