聚醚类离子载体是一类独特的具有广谱生物活性的聚酮化合物，在抗耐药菌、抗寄生虫、抗肿瘤方面极具开发潜力。目前已知的聚醚类离子载体无一例外均由放线菌产生，因此放线菌是这类活性物质的重要来源和生物合成研究的理想材料。
中科院微生物研究所微生物资源前期开发国家重点实验室黄英研究组通过对已知的聚醚类离子载体生物合成基因簇进行比较，发现其中均包含一个关键的后修饰酶基因——环氧化酶基因(epo)，该基因负责合成途径中不饱和聚醚中间体的环氧化反应。研究团队设计了该基因的特异引物，对逾千株来自不同生境和不同科属的放线菌进行了PCR筛选，结果表明，仅4个属的放线菌具有产生聚醚抗生素的潜力，而来自酸性土壤的嗜酸链霉菌最具潜力，所设计的引物也适合检测诸多基因簇未知的聚醚类离子载体产生菌的环氧化酶基因。随后对13株阳性菌株进行了产物分析，证实它们均产生聚醚类抗生素，且环氧化酶基因序列与聚醚产物结构之间具有明显的相关性，并获得了两个新结构类似物。由此建立了从放线菌中快速鉴别已知聚醚并发现未知聚醚的基因筛选策略。
该项研究提供了一个基于次级代谢生物合成后修饰酶基因筛选发现新天然产物的典型范例，对微生物资源的发掘利用具有指导意义。（生物谷Bioon.com）
生物谷推荐原文出处：
Applied and Environmental Microbiology DOI：10.1128/AEM.02915-10
Genetic Screening Strategy for Rapid Access to Polyether Ionophore Producers and Products in Actinomycetes
Hao Wang, Ning Liu, Lijun Xi, Xiaoying Rong, Jisheng Ruan, and Ying Huang
Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes.
