Secondary Metabolites of Two Novel Actinomycetes

78 Chinese Journal of Natural Medicines 2011, 9(1): 0078−0080 Chinese Journal of Natural Medicines

Cyclodipeptides from the Secondary Metabolites of Two Novel Actinomycetes

LIU Chao1, YANG Xue-Qiong1, DING Zhong-Tao 1, ZHAO Li-Xing2, CAO Yan-Ru2, XU Li-Hua2, YANG Ya-Bin 1*

1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology,

Yunnan University, Kunming 650091, China; 2Yunnan Institute of Microbiology, Yunnan University, Kunming 650091, China

Available online 20 Jan. 2011

[ABSTRACT] AIM: To investigate the secondary metabolites of two novel actinomycetes in order to find new compounds or effective components. METHODS: Compounds were isolated on silica gel column. The structures were elucidated on the basis of spectral data. RESULTS: Four cyclodipeptides were isolated from the fermentation broth of Sphaerisporangium album, and their structures were determined as cyclo (L-Pro-L-Asn) (1), cyclo (L-Pro-L-Ser) (2), cyclo (L-Pro-L-Ala) (3), and cyclo (L-Pro-L-Thr) (4). Three cyclodipeptides were isolated from the fermentation broth of Kribbella yunnanensis, and their structures were determined as cyclo (L-Pro-L-Ser) (2), cyclo (L-Pro-L-Thr) (4), and cyclo-di-Nδ-acetyl-L-ornithyl (5). CONCLUSION: 5 was a new natural compound.

The full assignments of 1H and 13C NMR chemical shifts for 1 and 5 were obtained by 2D NMR firstly. All compounds were isolated

from these two actinomycetes for the first time. When tested against tumor cell line panel (k563), 1 displayed cytotoxicity. [KEY WORDS] Peptides; Actinomycetes; Streptosporangium; Kribbella

[CLC Number] TQ46 [Document code] A [Article ID] 1672-3651(2011)01-0078-03

1 Introduction Many natural cyclopeptides have novel structures with significant bioactivity [1]. On the other hand, a growing

number of biologically active metabolites from actinomycete have been isolated during the last two decades [2-3]. As part of

our ongoing search for novel and potent antitumor natural products from actionomycetes, the chemical investigation on the cyclopeptides from the yeast of two actinomycetes was carried out. In this paper, we report the isolation and structural elucidation of five cyclic dipeptides isolated from two distinct bacterial strains. The novel species of Sphaerisporangium album designated YIM 48782, is a Gram-positive, aerobic

[Received on] 06-Sep-2010 [Research Funding] This project was supported by the State Key Program of National Natural Science Foundation of China (No. U0932601), the State Program of National Natural Science Foundation of China (No. 81060263) and National Undergraduate Innovative Experiment Program of China [*Corresponding author] YANG Ya-Bin: associate Prof., Tel: 86-871-5033719, E-mail: ybyang@ynu.edu.cn These authors have no any conflict of interest to declare. Copyright © 2011, China Pharmaceutical University. Published by Elsevier B.V. All rights reserved

actinomycete strain with antibacterial activity to Staphylococcus aureus. Purification by Silica gel column chromatography of the CHCl3-MeOH-soluble fractions of the

fermentation broths of Sphaerisporangium album gave cyclopeptide-containing fractions which were investigated by a TLC chemical detection method [4]. Four cyclodipeptides

1-4 were isolated from this strain. Besides a new natural cyclodipeptide (5), cyclodipeptides 2, 4 were also produced by the other novel species of the genus Kribbella, characterized as a Kribbella yunnanensis (YIM 30006). The full assignments of 1H and 13C NMR chemical shifts for 1

and 5 were obtained by 2D NMR firstly.

2 Experimental 2.1 General experimental procedures Silica gel (75-150 μm, 48-150 μm; Qingdao Marine Chemical Co., Ltd.) was used for column chromatography. Opticar rotations were measured with a Jasco DIP-370 digital polarimeter. 1D and 2D NMR spectra were obtained on a Bruker DRX-500 MHz instrument with TMS as internal standard. MS spectra were recorded with an Agilent G3250AA spectrometer and VG Autospec 3000. 2.2 Biological material and cultivation of actinomycelial strains