TY - JOUR
T1 - Terpenoids produced by actinomycetes
T2 - Isolation, structural elucidation and biosynthesis of new diterpenes, gifhornenolones A and B from Verrucosispora gifhornensis YM28-088
AU - Shirai, Masato
AU - Okuda, Masaaki
AU - Motohashi, Keiichiro
AU - Imoto, Masaya
AU - Furihata, Kazuo
AU - Matsuo, Yoshihide
AU - Katsuta, Atsuko
AU - Shizuri, Yoshikazu
AU - Seto, Haruo
N1 - Funding Information:
This work was supported by in part by a Grant-in-Aid for Scientific Research (B) to H Seto. We thank Professor T Ishikawa and Dr T Kumamoto of Chiba University for measurements of CD and ORD spectra. We also thank Dr T Kushiro of University of Tokyo for helpful discussion on the biosynthesis of gifhornenolone.
PY - 2010/5
Y1 - 2010/5
N2 - 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 Cglucose and U-13 C6 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 IC50 of 2.8 μg ml-1.
AB - 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 Cglucose and U-13 C6 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 IC50 of 2.8 μg ml-1.
KW - Androgen receptor binding inhibitor
KW - Biosynthesis
KW - Cyperusol C
KW - Gifhornenolone
KW - Terpenoid
KW - Verrucosispora gifhornensis
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U2 - 10.1038/ja.2010.30
DO - 10.1038/ja.2010.30
M3 - Article
C2 - 20379218
AN - SCOPUS:77952923683
VL - 63
SP - 245
EP - 250
JO - Journal of Antibiotics
JF - Journal of Antibiotics
SN - 0021-8820
IS - 5
ER -