Terpenoids produced by actinomycetes: isolation, structural elucidation and biosynthesis of new diterpenes, gifhornenolones A and B from Verrucosispora gifhornensis YM28-088.
New terpenoids named gifhornenolones A (1) and B (2) were isolated from the culture broth of Verrucosispora gifhornensis YM28-088, and their structures were established as hydroxylated isopimaradiene derivatives on the basis of extensive NMR and MS spectral analyses. In addition, a known sesquiterpene compound cyperusol C (3) was isolated. The absolute configuration of 1 was determined by nuclear Overhauser effect spectroscopy (NOESY) and CD spectra as 4R, 5S, 9R, 10S, 13R, and that of 2 was determined by NOESY experiments as 3R, 4R, 5R, 9R, 10S, 13R. Labeling experiments with [1-(13)C]glucose and [U-(13)C(6)]glucose confirmed that the MEP (2-C-methyl-D-erythritol-4-phosphate) pathway was used for the biosynthesis of terpenoids in this organism. 1 showed potent inhibitory activity to the androgen receptor with an IC(50) of 2.8 microg ml(-1).
Shirai
Masato
M
Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
Okuda
Masaaki
M
Motohashi
Keiichiro
K
Imoto
Masaya
M
Furihata
Kazuo
K
Matsuo
Yoshihide
Y
Katsuta
Atsuko
A
Shizuri
Yoshikazu
Y
Seto
Haruo
H
D039903:Actinobacteria / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular
D000900:Anti-Bacterial Agents; D004224:Diterpenes; C550111:gifhornenolone A; C550112:gifhornenolone B