A highly selective biosynthetic pathway to non-natural C 50 carotenoids assembled from moderately selective enzymes

Maiko Furubayashi, Mayu Ikezumi, Shinichi Takaichi, Takashi Maoka, Hisashi Hemmi, Takuya Ogawa, Kyoichi Saito, Alexander V. Tobias, Daisuke Umeno

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Synthetic biology aspires to construct natural and non-natural pathways to useful compounds. However, pathways that rely on multiple promiscuous enzymes may branch, which might preclude selective production of the target compound. Here, we describe the assembly of a six-enzyme pathway in Escherichia coli for the synthesis of C 50-astaxanthin, a non-natural purple carotenoid. We show that by judicious matching of engineered size-selectivity variants of the first two enzymes in the pathway, farnesyl diphosphate synthase (FDS) and carotenoid synthase (CrtM), branching and the production of non-target compounds can be suppressed, enriching the proportion of C 50 backbones produced. We then further extend the C 50 pathway using evolved or wild-type downstream enzymes. Despite not containing any substrate-or product-specific enzymes, the resulting pathway detectably produces only C 50 carotenoids, including ∼90% C50-astaxanthin. Using this approach, highly selective pathways can be engineered without developing absolutely specific enzymes.

Original languageEnglish
Article number7534
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Jul 14
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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