Biotransformation of gallic acid by Beauveria sulfurescens ATCC 7159.
Preparative-scale fermentation of gallic acid (3,4,5-trihydroxybenzoic acid) (1) with Beauveria sulfurescens ATCC 7159 gave two new glucosidated compounds, 4-(3,4-dihydroxy-6-hydroxymethyl-5-methoxy-tetrahydro-pyran-2-yloxy)-3-hydroxy-5-methoxy-benzoic acid (4), 3-hydroxy-4,5-dimethoxy-benzoic acid 3,4-dihydroxy-6-hydroxymethyl-5-methoxy-tetrahydro-pyran-2-yl ester (7), along with four known compounds, 3-O-methylgallic acid (2), 4-O-methylgallic acid (3), 3,4-O-dimethylgallic acid (5), and 3,5-O-dimethylgallic acid (6). The new metabolite genistein 7-O-beta-D-4''-O-methyl-glucopyranoside (8) was also obtained as a byproduct due to the use of soybean meal in the fermentation medium. The structural elucidation of the metabolites was based primarily on 1D-, 2D-NMR, and HRFABMS analyses. Among these compounds, 2, 3, and 5 are metabolites of gallic acid in mammals. This result demonstrated that microbial culture parallels mammalian metabolism; therefore, B. sulfurescens might be a useful tool for generating mammalian metabolites of related analogs of gallic acid (1) for complete structural identification and for further use in investigating pharmacological and toxicological properties in this series of compounds. In addition, a GRE (glucocorticoid response element)-mediated luciferase reporter gene assay was used to initially screen for the biological activity of the 6 compounds, 2-6 and 8, along with 1 and its chemical O-methylated derivatives 9-13. Among the 12 compounds tested, 11-13 were found to be significant, but less active than the reference compounds of methylprednisolone and dexamethasone.
Hsu
Feng-Lin
FL
Graduate Institute of Pharmacognosy Science, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei, 110, Taiwan.
Yang
Li-Ming
LM
Chang
Shwu-Fen
SF
Wang
Li-Hsuan
LH
Hsu
Chung-Yi
CY
Liu
Pan-Chun
PC
Lin
Shwu-Jiuan
SJ
D052982:Beauveria / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D005285:Fermentation; D005707:Gallic Acid / Q000378:metabolism*; D017930:Genes, Reporter; D008156:Luciferases / Q000096:biosynthesis; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014162:Transfection
D005707:Gallic Acid; D008156:Luciferases