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Enzymatic synthesis of benzylisoquinoline alkaloids using a parallel cascade strategy and tyrosinase variants

Author

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  • Yu Wang

    (University College London)

  • Fabiana Subrizi

    (University College London)

  • Eve M. Carter

    (University College London)

  • Tom D. Sheppard

    (University College London)

  • John M. Ward

    (University College London)

  • Helen C. Hailes

    (University College London)

Abstract

Benzylisoquinoline alkaloid derived pharmaceuticals are widely applied in modern medicines. Recent studies on the microbial production of benzylisoquinolines have highlighted key biological syntheses towards these natural products. Routes to non-natural benzylisoquinolines have been less explored, particularly halogenated compounds which are more challenging. Here, we show the use of a tyrosinase, tyrosine decarboxylase, transaminase, and norcoclaurine synthase which are combined in a parallel cascade design, in order to generate halogenated benzylisoquinoline alkaloids in high enantiomeric excess. Notably, mutagenesis studies are applied to generate tyrosinase mutants, which enhance the acceptance of halogenated tyrosines for use in the biocatalytic cascades developed.

Suggested Citation

  • Yu Wang & Fabiana Subrizi & Eve M. Carter & Tom D. Sheppard & John M. Ward & Helen C. Hailes, 2022. "Enzymatic synthesis of benzylisoquinoline alkaloids using a parallel cascade strategy and tyrosinase variants," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33122-1
    DOI: 10.1038/s41467-022-33122-1
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    References listed on IDEAS

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    1. Akira Nakagawa & Eitaro Matsumura & Takashi Koyanagi & Takane Katayama & Noriaki Kawano & Kayo Yoshimatsu & Kenji Yamamoto & Hidehiko Kumagai & Fumihiko Sato & Hiromichi Minami, 2016. "Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli," Nature Communications, Nature, vol. 7(1), pages 1-8, April.
    2. Akira Nakagawa & Hiromichi Minami & Ju-Sung Kim & Takashi Koyanagi & Takane Katayama & Fumihiko Sato & Hidehiko Kumagai, 2011. "A bacterial platform for fermentative production of plant alkaloids," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
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