Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 3 Taicheng Road, Yangling, 712100, Shaanxi, China; College of Innovation and Experiment, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi, 712100, China.
State Key Laboratory of Stress Biology for Arid Areas, Northwest A&F University, Yangling, Shaanxi, China.
Microbiol Res. 2021 Mar;244:126652. doi: 10.1016/j.micres.2020.126652. Epub 2020 Dec 1.
Actinobacteria that inhabit lichen symbionts are considered a promising yet previously underexplored source of novel compounds. Here, for the first time, we conducted a comprehensive investigation with regard to strain isolation and identification of lichen-associated actinobacteria from Tibet Plateau, antimicrobial activity screening, biosynthetic genes detection, bioactive metabolites identification and activity prediction. A large number of culturable actinomycetes were isolated from lichens around Qinghai Lake, in Qinghai-Tibet Plateau. Twenty-seven strains with distinct morphological characteristics were preliminarily studied. 16S rRNA gene identification showed that 13 strains were new species. The PCR-screening of specific biosynthetic genes indicated that these 27 isolates had abundant intrinsic biosynthetic potential. The antimicrobial activity experiment screened out some potential biological control antagonistic bacteria. The metabolites of 13 strains of Streptomyces with antibacterial activity were analyzed by LC-HRMS, and further 18 compounds were identified by NMR and / or LC-HRMS. The identified compounds were mainly pyrrolidine and indole derivatives, as well as anthracyclines. Seven compounds were identified with less biological activity, then predicted and evaluated their biological activity. The predicted results showed that compound 2 had excellent inhibitory activity on HIV-1 reverse transcriptase. Overall, the results indicate actinobacteria isolated from unexploited plateau lichen are promising sources of biological active metabolite, which could provide important bioactive compounds as potential antibiotic drugs.
栖息在共生地衣中的放线菌被认为是一种很有前途但尚未得到充分探索的新型化合物来源。在这里,我们首次对青藏高原地衣相关放线菌进行了全面的菌株分离和鉴定、抗菌活性筛选、生物合成基因检测、生物活性代谢物鉴定和活性预测。从青藏高原青海湖周围的地衣中分离到大量可培养的放线菌。对 27 株具有明显形态特征的菌株进行了初步研究。16S rRNA 基因鉴定表明,其中 13 株为新种。对特定生物合成基因的 PCR 筛选表明,这 27 个分离株具有丰富的内在生物合成潜力。抗菌活性实验筛选出了一些有潜在生物防治作用的拮抗菌。对具有抗菌活性的 13 株链霉菌的代谢产物进行了 LC-HRMS 分析,并通过 NMR 和/或 LC-HRMS 进一步鉴定了 18 种化合物。鉴定的化合物主要为吡咯烷和吲哚衍生物以及蒽环类化合物。有 7 种化合物的生物活性较低,然后对其进行了预测和评价。预测结果表明,化合物 2 对 HIV-1 逆转录酶具有极好的抑制活性。总的来说,这些结果表明,从未开发的高原地衣中分离出的放线菌是具有生物活性代谢物的有前途的来源,可为潜在的抗生素药物提供重要的生物活性化合物。