Biotransformation of (-)-α-Bisabolol by Absidia coerulea.

Jisu Park,Ik-Soo Lee,Fubo Han

doi:10.3390/molecules27030881

Abstract

(−)-α-Bisabolol, a bioactive monocyclic sesquiterpene alcohol, has been used in pharmaceutical and cosmetic products with anti-inflammatory, antibacterial and skin-caring properties. However, the poor water solubility of (−)-α-bisabolol limits its pharmaceutical applications. It has been recognized that microbial transformation is a very useful approach to generate more polar metabolites. Fifteen microorganisms were screened for their ability to metabolize (−)-α-bisabolol in order to obtain its more polar derivatives, and the filamentous fungus Absidia coerulea was selected for scale-up fermentation. Seven new and four known metabolites were obtained from biotransformation of (−)-α-bisabolol (1), and all the metabolites exhibited higher aqueous solubility than that of the parent compound 1. The structures of newly formed metabolites were established as (1R,5R,7S)- and (1R,5S,7S)-5-hydroxy-α-bisabolol (2 and 3), (1R,5R,7S,10S)-5-hydroxybisabolol oxide B (4), (1R,7S,10S)-1-hydroxybisabolol oxide B (5), 12-hydroxy-α-bisabolol (7), (1S,3R,4S,7S)- and (1S,3S,4S,7S)-3,4-dihydroxy-α-bisabolol (8 and 10) on the basis of spectroscopic analyses. These compounds could also be used as reference standards for the detection and identification of the metabolic products of 1 in the mammalian system.

Highlights

Introduction(−)-α-Bisabolol (1), a natural monocyclic sesquiterpene alcohol known as levomenol, has been found in essential oils of various plants such as Matricaria recutita and Alpinia officinarum Hance [1,2]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
(−)-α-Bisabolol (1), a natural monocyclic sesquiterpene alcohol known as levomenol, has been found in essential oils of various plants such as Matricaria recutita and Alpinia officinarum Hance [1,2]

Summary

Introduction

(−)-α-Bisabolol (1), a natural monocyclic sesquiterpene alcohol known as levomenol, has been found in essential oils of various plants such as Matricaria recutita and Alpinia officinarum Hance [1,2]. The presence of the tetrahydrofuran ring was evident from the oxymethine signal at δH 3.68, two non-equivalent methylene signals at δH 1.85/1.62 and 1.83/1.78, together with three oxygenated carbon signals at δH 84.4, 86.1 and 70.5 These elucidations were supported by the long-range correlations from H-3/6/15 to C-5, from H-8/12/13 to C-11, from H-14 to C-1, and from H-9 to C-7 in the HMBC spectrum of 4 (Figure 4). Fermentation experiments were performed in three types of media: A. coerulea, A. alternata, A. fumigatus, M. hiemalis, P. chrysogenum and T. koningii were incubated on malt medium (malt extract 20 g/L, D-glucose 20 g/L, peptone 1 g/L); F. neoformans, K. marxianus, and M. lacticum were cultured on yeast-malt medium (D-glucose 10 g/L, peptone 5 g/L, malt extract 3 g/L, and yeast extract 3 g/L); other microorganisms were cultured on potato dextrose medium (potato dextrose broth 24 g/L)

Screening Procedures

Extraction and Isolation of Metabolites

Conclusions