Microbial metabolism of steviol and steviol-16α,17-epoxide

Li Ming Yang, Feng-Lin Hsu, Shwu Fen Chang, Juei Tang Cheng, Ju Yin Hsu, Chung-Yi Hsu, Pan Chun Liu, Shwu Jiuan Lin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7α,11β,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7α,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-α-d-glucopyranosyl ester (4), ent-13,16β,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16α,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11α,13,16α,17-tetrahydroxykauran-19-oic acid (10), ent-1β,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7α,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16β-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11β,13-dihydroxy-16β,17-epoxykauran-19-oic acid (12), and ent-11β,13,16β,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

Original languageEnglish
Pages (from-to)562-570
Number of pages9
JournalPhytochemistry
Volume68
Issue number4
DOIs
Publication statusPublished - Feb 2007

Fingerprint

steviol
Epoxy Compounds
epoxides
Metabolism
Acids
metabolism
acids
Metabolites
metabolites
glucocorticoids
Glucocorticoids
Bacillus megaterium
Mucor
Aspergillus niger
Poisons
glycemic effect
Biotransformation
Aspergillus
Luciferases
Hypoglycemic Agents

Keywords

  • Diterpenoid
  • Microbial transformation
  • Steviol
  • Steviol-16α,17-epoxide

ASJC Scopus subject areas

  • Plant Science
  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery

Cite this

Microbial metabolism of steviol and steviol-16α,17-epoxide. / Yang, Li Ming; Hsu, Feng-Lin; Chang, Shwu Fen; Cheng, Juei Tang; Hsu, Ju Yin; Hsu, Chung-Yi; Liu, Pan Chun; Lin, Shwu Jiuan.

In: Phytochemistry, Vol. 68, No. 4, 02.2007, p. 562-570.

Research output: Contribution to journalArticle

Yang, LM, Hsu, F-L, Chang, SF, Cheng, JT, Hsu, JY, Hsu, C-Y, Liu, PC & Lin, SJ 2007, 'Microbial metabolism of steviol and steviol-16α,17-epoxide', Phytochemistry, vol. 68, no. 4, pp. 562-570. https://doi.org/10.1016/j.phytochem.2006.11.021
Yang, Li Ming ; Hsu, Feng-Lin ; Chang, Shwu Fen ; Cheng, Juei Tang ; Hsu, Ju Yin ; Hsu, Chung-Yi ; Liu, Pan Chun ; Lin, Shwu Jiuan. / Microbial metabolism of steviol and steviol-16α,17-epoxide. In: Phytochemistry. 2007 ; Vol. 68, No. 4. pp. 562-570.
@article{faeba1f484d0459cacbf36bcfe241c47,
title = "Microbial metabolism of steviol and steviol-16α,17-epoxide",
abstract = "Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7α,11β,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7α,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-α-d-glucopyranosyl ester (4), ent-13,16β,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16α,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11α,13,16α,17-tetrahydroxykauran-19-oic acid (10), ent-1β,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7α,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16β-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11β,13-dihydroxy-16β,17-epoxykauran-19-oic acid (12), and ent-11β,13,16β,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.",
keywords = "Diterpenoid, Microbial transformation, Steviol, Steviol-16α,17-epoxide",
author = "Yang, {Li Ming} and Feng-Lin Hsu and Chang, {Shwu Fen} and Cheng, {Juei Tang} and Hsu, {Ju Yin} and Chung-Yi Hsu and Liu, {Pan Chun} and Lin, {Shwu Jiuan}",
year = "2007",
month = "2",
doi = "10.1016/j.phytochem.2006.11.021",
language = "English",
volume = "68",
pages = "562--570",
journal = "Phytochemistry",
issn = "0031-9422",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Microbial metabolism of steviol and steviol-16α,17-epoxide

AU - Yang, Li Ming

AU - Hsu, Feng-Lin

AU - Chang, Shwu Fen

AU - Cheng, Juei Tang

AU - Hsu, Ju Yin

AU - Hsu, Chung-Yi

AU - Liu, Pan Chun

AU - Lin, Shwu Jiuan

PY - 2007/2

Y1 - 2007/2

N2 - Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7α,11β,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7α,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-α-d-glucopyranosyl ester (4), ent-13,16β,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16α,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11α,13,16α,17-tetrahydroxykauran-19-oic acid (10), ent-1β,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7α,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16β-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11β,13-dihydroxy-16β,17-epoxykauran-19-oic acid (12), and ent-11β,13,16β,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

AB - Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7α,11β,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7α,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-α-d-glucopyranosyl ester (4), ent-13,16β,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16α,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11α,13,16α,17-tetrahydroxykauran-19-oic acid (10), ent-1β,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7α,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16β-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11β,13-dihydroxy-16β,17-epoxykauran-19-oic acid (12), and ent-11β,13,16β,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

KW - Diterpenoid

KW - Microbial transformation

KW - Steviol

KW - Steviol-16α,17-epoxide

UR - http://www.scopus.com/inward/record.url?scp=33846560654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846560654&partnerID=8YFLogxK

U2 - 10.1016/j.phytochem.2006.11.021

DO - 10.1016/j.phytochem.2006.11.021

M3 - Article

C2 - 17207824

AN - SCOPUS:33846560654

VL - 68

SP - 562

EP - 570

JO - Phytochemistry

JF - Phytochemistry

SN - 0031-9422

IS - 4

ER -