Molecular breeding of carotenoid biosynthetic pathways

Claudia Schmidt-Dannert*, Daisuke Umeno, Frances H. Arnold

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

280 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)750-753
Number of pages4
JournalNature biotechnology
Volume18
Issue number7
DOIs
Publication statusPublished - 2000 Jul
Externally publishedYes

Keywords

  • Carotenoid
  • In vitro evolution
  • Metabolic engineering
  • Molecular breeding

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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