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Molecular breeding of carotenoid biosynthetic pathways

Schmidt-Dannert, Claudia and Umeno, Daisuke and Arnold, Frances H. (2000) Molecular breeding of carotenoid biosynthetic pathways. Nature Biotechnology, 18 (7). pp. 750-753. ISSN 1087-0156. https://resolver.caltech.edu/CaltechAUTHORS:20150407-151935752

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Abstract

The burgeoning demand for complex, biologically active molecules for medicine, materials science, consumer products, and agrochemicals is driving efforts to engineer new biosynthetic pathways into microorganisms and plants. We have applied principles of breeding, including mixing genes and modifying catalytic functions by in vitro evolution, to create new metabolic pathways for biosynthesis of natural products in Escherichia coli. We expressed shuffled phytoene desaturases in the context of a carotenoid biosynthetic pathway assembled from different bacterial species and screened the resulting library for novel carotenoids. One desaturase chimera efficiently introduced six rather than four double bonds into phytoene, to favor production of the fully conjugated carotenoid, 3,4,3',4'-tetradehydrolycopene. This new pathway was extended with a second library of shuffled lycopene cyclases to produce a variety of colored products. One of the new pathways generates the cyclic carotenoid torulene, for the first time, in E. coli. This combined approach of rational pathway assembly and molecular breeding may allow the discovery and production, in simple laboratory organisms, of new compounds that are essentially inaccessible from natural sources or by synthetic chemistry.


Item Type:Article
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http://dx.doi.org/10.1038/77319DOIArticle
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ORCID:
AuthorORCID
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2000 Nature America Inc. Received 30 March 2000; accepted 10 May 2000. We are grateful to Dr. Peter G. Green (Environmental Analysis Center, Caltech) for technical support and helpful discussions on mass analysis. C.S.-D. was supported by the Deutsche Forschungsgemeinschaft (DFG) and D.U. by the Japan Society for the Promotion of Science (JSPS).
Funders:
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Japan Society for the Promotion of Science (JSPS)UNSPECIFIED
Subject Keywords:carotenoid, molecular breeding, metabolic engineering, in vitro evolution
Issue or Number:7
Record Number:CaltechAUTHORS:20150407-151935752
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150407-151935752
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:56446
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:07 Apr 2015 22:36
Last Modified:03 Oct 2019 08:13

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