Novel ent-Beyeran-19-oic Acids from Biotransformations of Isosteviol Metabolites by Mortierella isabellina

Abstract

Biotransformations of ent-16β-hydroxybeyeran-19-oic acid (1) by Mortierella isabellina produced hydroxylated metabolites. The isolated metabolites included three new compounds, ent-14β,16β-dihydroxybeyeran-19-oic acid (3), ent-12β-hydroxy-16-oxobeyeran-19-oic acid (4), and ent-7α,12β-dihydroxy-16-oxobeyeran-19-oic acid (5), and one known compound, ent-7α,16β-dihydroxybeyeran-19-oic acid (2). The structural elucidation was achieved by detailed analysis of LC-MS chromatograms, and MS and NMR spectroscopic data. In this study, M. isabellina hydroxylated the basic skeleton beyeran-19-oic acid at the 7β-, 12α-, and 14α-positions, and oxidized the skeleton at the 16-position. All compounds were evaluated with the cell viability assay. The results of the bioassay indicated that MTT formazan exocytosis occurs upon treatment of the cells with 1.

Key words

ent-16β-Hydroxybeyeran-19-oic acid - Mortierella isabellina - microbial biotransformations - hydroxylation - stevioside - isoteviol - MTT formazan exocytosis

References

• 1 Oliveira B H, Santos M C, Leal P C. Biotransformation of the diterpenoid, isosteviol, by Aspergillus niger, Penicillium chrysogenum and Rhizopus arrhizus .  Phytochemistry. 1999;  51 737-41.
• 2 Hanson J R. The microbiological transformation of diterpenoids.  Nat Prod Rep. 1992;  9 139-52.
• 3 Atta-ur-Rahman , Farooq A, Choudhary M I. Microbial transformation of sclareolide.  J Nat Prod. 1997;  60 1038-40.
• 4 Yang L M, Hsu F L, Cheng J T, Chang C H, Liu P C, Lin S J. Hydroxylation and glucosidation of ent-16β-hydroxybeyeran-19-oic acid by Bacillus megaterium and Aspergillus niger .  Planta Med. 2004;  70 359-6.
• 5 Hou C C. Studies on the active compounds from Bacopa monniera, Lactuca indica, and Stevia rebaudiana. [dissertation]. Taipei; Taipei Medical University 2003.
• 6 Lee C N, Wong K L, Liu J C, Chen Y J, Cheng J T, Chan P. Inhibitory effect of stevioside on calcium influx to produce antihypertension.  Planta Med. 2001;  67 796-9.
• 7 Ali H S, Hanson J R, de Oliveira B H. The biotransformation of some ent-beyeran-19-oic acids by Gibberella fujikuroi .  Phytochemistry. 1992;  31 507-10.
• 8 Abourashed E A, Clark A M, Hufford C D. Microbial models of mammalian metabolism of xenobiotics: An updated review.  Curr Med Chem. 1999;  6 359-74.
• 9 Diana J, Govaerts C, Hoogmartens J, VanSchepdael A, Adams E. Charaterization of impurities in dirithromycin by liquid chromatography/ion trap mass spectrometry.  J Chromatogr A. 2006;  1125 52-66.
• 10 Wan E CH, Yu J Z. Determination of sugar compounds in atmospheric aerosols by liquid chromatography combined with positive electrospray ionization mass spectrometry.  J Chromatogr A. 2006;  1107 175-81.
• 11 Hsu F L, Hou C C, Yang L M. Microbial transformations of isosteviol.  J Nat Prod. 2002;  65 273-7.
• 12 Chang C H, Lin S J. Microbial transformations of steviol and ent-16β-hydroxybeyeran-19-oic acid. [dissertation]. Taipei; Taipei Medical University 2002.
• 13 Huang S X, Zhao Q S, Xu G, Wiao W L, Li R T, Hou A J. et al . ent-Kaurane diterpenoids from Isodon albopilosus .  J Nat Prod. 2005;  68 1758-62.
• 14 Xian M, Kang Y, Yan J, Liu J, Bi Y, Zhen K. Production of linolenic acid by Mortierella isabellina grown on octadecanol.  Curr Microbiol. 2002;  44 141-4.
• 15 Liu Y, Peterson D A, Schubert D. Amyloid β peptide alters intracellular vesicle trafficking and cholesterol homeostasis.  Proc Natl Acad Sci USA. 1998;  95 13 266-71.
• 16 Slater T F, Sawyer B, Strauli U. Studies on succinate-tetrazolium reductase system III: points of coupling of four tetrazolium salts.  Biochim Biophys Acta. 1963;  77 383-93.
• 17 Liu Y, Peterson D A, Kimura H, Schubert D. Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction.  J Neurochem. 1997;  69 581-93.
• 18 Hertel C, Hauser N, Schubenel R, Seilheimer B, Kemp J. A β-amyloid-induced cell toxicity: enhancement of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-dependent cell death.  J Neurochem. 1996;  67 272-6.
• 19 Abe K, Saito H. Cholesterol does not affect the toxicity of amyloid β fragment but mimics it effect on MTT formazan exocytosis in cultured rat hippocampal neurons.  Neurosci Res. 1999;  35 165-74.