Multifactorial optimization enables the identification of a greener method to produce (+)-nootkatone

J Biotechnol. 2024 Sep 20:393:41-48. doi: 10.1016/j.jbiotec.2024.07.008. Epub 2024 Jul 14.

Abstract

The natural aroma compound (+)-nootkatone was obtained in selective conversions of up to 74 mol% from inexpensive (+)-valencene substrate by using a comparatively greener biocatalytic process developed based on modifications of the previously published Firmenich method. Buffer identity and concentration, pH, temperature and downstream work-up procedures were optimized to produce a crude product in which >90 % of (+)-valencene had been converted, with high chemoselectivity observed for (+)-nootkatone production. Interestingly, the biotransformation was carried out efficiently at temperatures as low as 21 ºC. Surprisingly, the best results were obtained when an acidic pH in the range of 3-6 was applied, as compared to the previously published procedure in which it appeared to be necessary to buffer the pH optimally and fixed throughout at 8.5. Furthermore, there was no need to maintain a pure oxygen atmosphere to achieve good (+)-nootkatone yields. Instead, air bubbled continuously at a low rate through the reaction mixture via a submerged glass capillary was sufficient to enable the desired lipoxygenase-catalyzed oxidation reactions to occur efficiently. No valencene epoxide side-products were detected in the organic product extract by a standard GCMS protocol. Only traces of the anticipated corresponding α- and β-nootkatol intermediates were routinely observed.

Keywords: Biocatalysis; Green process; Nootkatone; Soy bean lipoxygenase.

MeSH terms

  • Biocatalysis
  • Biotransformation
  • Green Chemistry Technology / methods
  • Hydrogen-Ion Concentration
  • Lipoxygenase / metabolism
  • Oxidation-Reduction
  • Polycyclic Sesquiterpenes* / chemistry
  • Sesquiterpenes* / chemistry
  • Sesquiterpenes* / metabolism
  • Temperature

Substances

  • nootkatone
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • valencene
  • Lipoxygenase