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新型芳香族聚酮类化合物来自土壤链霉菌属:纯化、表征和生物活性研究。

Novel aromatic polyketides from soil Streptomyces spp.: purification, characterization and bioactivity studies.

机构信息

Hislop School of Biotechnology, Hislop College, Nagpur, Maharashtra, 440001, India.

Department of Biochemistry, Dr. Ambedkar College, Deekshabhoomi, Nagpur, Maharashtra, 440001, India.

出版信息

World J Microbiol Biotechnol. 2018 Apr 24;34(5):67. doi: 10.1007/s11274-018-2448-1.

Abstract

Aromatic polyketides are important therapeutic compounds which include front line antibiotics and anticancer drugs. Since most of the aromatic polyketides are known to be produced by soil dwelling Streptomyces, 54 Streptomyces strains were isolated from the soil samples. Five isolates, R1, B1, R3, R5 and Y8 were found to be potent aromatic polyketide producers and were identified by 16S rRNA gene sequencing as Streptomyces spectabilis, Streptomyces olivaceus, Streptomyces purpurascens, Streptomyces coeruleorubidus and Streptomyces lavendofoliae respectively. Their sequences have been deposited in the GenBank under the accession numbers KF468818, KF681280, KF395224, KF527511 and KF681281 respectively. The Streptomyces strains were cultivated in the media following critically optimised culture conditions. The resulting broth extracts were fractionated on a silica gel column and preparative TLC to obtain pure compounds. The pure compounds were tested for bioactivity and the most potent compound from each isolate was identified by UV-Vis, IR and NMR spectroscopic methods. Isolated S. spectabilis (R1), yielded one potent compound identified as dihydrodaunomycin with an MIC of 4 µg/ml against Bacillus cereus and an IC value of 24 µM against HeLa. S. olivaceus (B1), yielded a comparatively less potent compound, elloramycin. S. purpurascens (R3) yielded three compounds, rhodomycin, epelmycin and obelmycin. The most potent compound was rhodomycin with an MIC of 2 µg/ml against B. cereus and IC of 15 µM against HeLa. S. coeruleorubidus (R5), yielded daunomycin showing an IC of 10 µM and also exhibiting antimetastatic properties against HeLa. S. lavendofoliae (Y8), yielded a novel aclacinomycin analogue with IC value of 2.9 µM and potent antimetastatic properties at 1 µM concentration against HeLa. The study focuses on the characterization of aromatic polyketides from soil Streptomyces spp., which can serve as potential candidates for development of chemotherapeutic drugs in future.

摘要

芳香族聚酮类化合物是重要的治疗化合物,包括一线抗生素和抗癌药物。由于大多数芳香族聚酮类化合物已知是由土壤居住的链霉菌产生的,因此从土壤样本中分离了 54 株链霉菌。发现五个分离株,R1、B1、R3、R5 和 Y8 是强效芳香族聚酮类化合物的产生者,并通过 16S rRNA 基因测序分别鉴定为壮观链霉菌、橄榄色链霉菌、紫色链霉菌、蓝色链霉菌和薰衣草色链霉菌。它们的序列已在 GenBank 中以 KF468818、KF681280、KF395224、KF527511 和 KF681281 的 accession numbers 进行了注册。链霉菌菌株在经过严格优化的培养条件下的培养基中进行培养。将所得发酵液在硅胶柱和制备 TLC 上进行分馏,以获得纯化合物。测试了纯化合物的生物活性,并通过 UV-Vis、IR 和 NMR 光谱方法鉴定了每个分离株中最有效的化合物。分离出的壮观链霉菌(R1)产生了一种强效化合物,被鉴定为二氢柔红霉素,对蜡状芽孢杆菌的 MIC 为 4μg/ml,对 HeLa 的 IC 值为 24μM。橄榄色链霉菌(B1)产生了一种相对较弱效的化合物,埃洛霉素。紫色链霉菌(R3)产生了三种化合物,罗红霉素、表霉素和奥贝霉素。最有效的化合物是罗红霉素,对蜡状芽孢杆菌的 MIC 为 2μg/ml,对 HeLa 的 IC 为 15μM。蓝色链霉菌(R5)产生了柔红霉素,其 IC 为 10μM,并且对 HeLa 也表现出抗转移特性。薰衣草色链霉菌(Y8)产生了一种新型阿克拉霉素类似物,其 IC 值为 2.9μM,在 1μM 浓度下对 HeLa 具有很强的抗转移特性。该研究侧重于从土壤链霉菌中表征芳香族聚酮类化合物,这些化合物可以作为未来开发化疗药物的潜在候选物。

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