Original Article | Published:

Biosynthetic potential of sesquiterpene synthases: product profiles of Egyptian Henbane premnaspirodiene synthase and related mutants

The Journal of Antibiotics volume 69, pages 524533 (2016) | Download Citation

Abstract

The plant terpene synthase (TPS) family is responsible for the biosynthesis of a variety of terpenoid natural products possessing diverse biological functions. TPSs catalyze the ionization and, most commonly, rearrangement and cyclization of prenyl diphosphate substrates, forming linear and cyclic hydrocarbons. Moreover, a single TPS often produces several minor products in addition to a dominant product. We characterized the catalytic profiles of Hyoscyamus muticus premnaspirodiene synthase (HPS) and compared it with the profile of a closely related TPS, Nicotiana tabacum 5-epi-aristolochene synthase (TEAS). The profiles of two previously studied HPS and TEAS mutants, each containing nine interconverting mutations, dubbed HPS-M9 and TEAS-M9, were also characterized. All four TPSs were compared under varying temperature and pH conditions. In addition, we solved the X-ray crystal structures of TEAS and a TEAS quadruple mutant complexed with substrate and products to gain insight into the enzymatic features modulating product formation. These informative structures, along with product profiles, provide new insight into plant TPS catalytic promiscuity.

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Acknowledgements

Research in our laboratories is supported by NSF EEC-0813570 to JPN and NSF IOS1516156 to MDB. JPN is an investigator with the Howard Hughes Medical Institute.

Author information

Author notes

    • Hyun Jo Koo
    •  & Christopher R Vickery

    Co-first authors.

Affiliations

  1. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Jack H Skirball Center for Chemical Biology and Proteomics, La Jolla, CA, USA

    • Hyun Jo Koo
    • , Christopher R Vickery
    • , Yi Xu
    • , Gordon V Louie
    • , Paul E O'Maille
    • , Marianne Bowman
    • , Charisse M Nartey
    •  & Joseph P Noel
  2. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA

    • Christopher R Vickery
    •  & Michael D Burkart

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The authors declare no conflict of interest.

Corresponding authors

Correspondence to Hyun Jo Koo or Joseph P Noel.

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DOI

https://doi.org/10.1038/ja.2016.68

Supplementary Information accompanies the paper on The Journal of Antibiotics website (http://www.nature.com/ja)

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