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Novel hydroxycarotenoids with improved antioxidative properties produced by gene combination in Escherichia coli

Nature Biotechnology volume 18, pages 843–846 (2000)Cite this article

Abstract

We have used combinatorial biosynthesis to synthesize novel lipophilic carotenoids that are powerful cellular antioxidants. By co-expressing three different carotenoid desaturases in combination with a carotenoid hydratase, a cyclase, and a hydroxylase on compatible plasmids in Escherichia coli, we synthesized four novel carotenoids not previously detected in biological material or chemically synthesized. Their identification was based on their relative retention times on HPLC, spectroscopic properties, molecular weights, number of hydroxy groups, and 1H-NMR spectra. The carotenoids were designated as 1-HO-3′, 4′-didehydrolycopene, 3, 1′-(HO)2-γ-carotene, 1,1′-(HO)2-3, 4, 3′, 4′-tetradehydrolycopene, and 1, 1′-(HO)2-3, 4-didehydrolycopene. These novel acyclic derivatives differ from structurally related compounds by extension of the conjugated polyene chain as well as additional hydroxy groups at position C-1′. We determined their antioxidative activity in a liposome-membrane model system, which showed that their ability to protect against photooxidation and radical-mediated peroxidation reactions was linked to the length of the conjugated double-bond system and the presence of a single hydroxy group. The protection of membrane degradation was superior to the related 1-HO and 1, 1′-(HO)2 lycopene derivatives, making them interesting pharmaceutical candidates.

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Figure 1: HPLC separation of carotenoids from the E. coli transformants JM101/pACCRT-EBal-1/pRKCRT-C (A), JM101/pACCAR25ΔcrtX/pRKCRT-C (B), and JM101/pACCRT-EBIEU/pRKCRT-C/pQECRT-D (C).
Figure 2: Reaction sequence for the formation of new hydroxy carotenoids in E. coli transformants.

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Authors and Affiliations

  1. Botanisches Institut, Goethe Universität, P.O. Box 111932, Frankfurt, D-60054, Germany

    Manuela Albrecht, Sabine Steiger & Gerhard Sandmann

  2. Biological Laboratory, Nippon Medical School, Kawasaki, 211-0063, Japan

    Shinichi Takaichi

  3. Department of Biochemistry and Engineering, Tohoku University, Sendai, 980-8577, Japan

    Zheng-Yu Wang

Authors
  1. Manuela Albrecht
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  2. Shinichi Takaichi
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  3. Sabine Steiger
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  4. Zheng-Yu Wang
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  5. Gerhard Sandmann
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Correspondence to Gerhard Sandmann.

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Albrecht, M., Takaichi, S., Steiger, S. et al. Novel hydroxycarotenoids with improved antioxidative properties produced by gene combination in Escherichia coli. Nat Biotechnol 18, 843–846 (2000). https://doi.org/10.1038/78443

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