Please use this identifier to cite or link to this item: https://doi.org/10.1002/bit.25123
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dc.titleCombinatorial engineering of mevalonate pathway for improved amorpha-4,11-diene production in budding yeast
dc.contributor.authorYuan, J.
dc.contributor.authorChing, C.B.
dc.date.accessioned2014-10-09T06:44:57Z
dc.date.available2014-10-09T06:44:57Z
dc.date.issued2014-03
dc.identifier.citationYuan, J., Ching, C.B. (2014-03). Combinatorial engineering of mevalonate pathway for improved amorpha-4,11-diene production in budding yeast. Biotechnology and Bioengineering 111 (3) : 608-617. ScholarBank@NUS Repository. https://doi.org/10.1002/bit.25123
dc.identifier.issn00063592
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/88669
dc.description.abstractCombinatorial genome integration of mevalonate pathway genes was performed with the aim of optimizing the metabolic flux for improved production of terpenoids in budding yeast. In the present study, we developed a novel δ-integration platform to achieve multiple genome integrations through modulating the concentration of antibiotics. By exploiting carotenoid biosynthesis as screening module, we successfully created a library of yeast colonies appeared with various intensities of orange color. As proof-of-concept that carotenoid overproducers could serve to boost the titer of other terpenoids, we further tested engineered strains for the production of amorpha-4,11-diene, an important precursor for antimalarial drug. However, we experienced some limitations of the carotenoid-based screening approach as it was only effective in detecting a small range of pathway activity improvement and further increasing mevalonate pathway activity led to a decreased orange color. By far, we were only able to obtain one mutant strain yielded more than 13-fold amorpha-4,11-diene over parental strains, which was approximately 64mg/L of caryophyllene equivalents. Further qPCR studies confirmed that erg10, erg13, thmg1 and erg12 involved in mevalonate pathway were overexpressed in this mutant strain. We envision the current δ-integration platform would form the basis of a generalized technique for multiple gene integrations in yeast-a method that would be of significant interest to the metabolic engineering community. Biotechnol. Bioeng. 2014;111: 608-617. © 2013 Wiley Periodicals, Inc.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1002/bit.25123
dc.sourceScopus
dc.subjectCarotenoids
dc.subjectCombinatorial engineering
dc.subjectMevalonate pathway
dc.subjectPathway activity improvement
dc.subjectSaccharomyces cerevisiae
dc.subjectSesquiterpene
dc.typeArticle
dc.contributor.departmentCHEMICAL & BIOMOLECULAR ENGINEERING
dc.description.doi10.1002/bit.25123
dc.description.sourcetitleBiotechnology and Bioengineering
dc.description.volume111
dc.description.issue3
dc.description.page608-617
dc.description.codenBIBIA
dc.identifier.isiut000331059500018
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