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.

居住在地衣共生体中的放线菌被认为是一种有前途但以前未充分开发的新型化合物来源。在此，我们首次从青藏高原地衣相关放线菌的菌株分离鉴定、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等方面进行了综合研究。从青藏高原青海湖周围的地衣中分离出大量可培养的放线菌。初步研究了27株具有明显形态特征的菌株。16S rRNA基因鉴定结果显示13株为新种。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潜在的生控拮抗细菌。13个菌株的代谢物具有抗菌活性的链霉菌通过 LC-HRMS 进行了分析，另外 18 种化合物通过 NMR 和/或 LC-HRMS 进行了鉴定。鉴定的化合物主要是吡咯烷和吲哚衍生物，以及蒽环类。鉴定了七种生物活性较低的化合物，然后预测并评估了它们的生物活性。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。总体而言，结果表明从未开发的高原地衣中分离出的放线菌是生物活性代谢物的有希望的来源，可以提供重要的生物活性化合物作为潜在的抗生素药物。