The Key Laboratory of Oasis Agricultural Pest Management and Plant Protection Utilization, College of Agriculture, Shihezi University, Shihezi 832003, China.
Molecules. 2024 Apr 28;29(9):2040. doi: 10.3390/molecules29092040.
Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against , with an EC value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against , with an EC value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.
放线菌一直被认为是抗菌天然产物的重要来源。近年来，极端环境中的放线菌已成为主要研究方向之一。KN37 是从新疆喀纳斯寒冷地区分离得到的，具有很强的抗菌活性，但主要活性化合物尚不清楚。因此，我们旨在结合基因组学和传统分离方法从菌株 KN37 中获得生物活性化合物。全基因组测序和 KEGG 富集分析表明，KN37 具有合成次生代谢产物的潜力，预测到 41 个生物合成基因簇，其中一些与负责合成抗菌抗生素的已知基因簇具有高度相似性。采用传统分离方法和活性导向分离，从菌株 KN37 的发酵液中分离纯化出 7 种具有较强生物活性的化合物。这些化合物被鉴定为 4-(二乙氨基)水杨醛（1）、4-亚硝基二苯胺（2）、N-(2,4-二甲基苯基)甲酰胺（3）、4-硝基邻苯二酚（4）、丁二酸（5）、苯乳酸（6）和 5,6-二甲基苯并咪唑（7）。此外，4-(二乙氨基)水杨醛对 的抑制作用最强，EC 值为 14.487mg/L，而 4-亚硝基二苯胺对 的抗菌活性最强，EC 值为 5.715mg/L。本研究成功地从菌株 KN37 的代谢产物中分离出几种具有高抗菌活性的化合物，可作为后续化学合成的支架。另一方面，新预测的抗生素样物质尚未被分离出来，但它们仍然具有重要的研究价值。它们对研究活性天然产物生物合成途径、沉默基因簇的激活以及工程菌的构建具有指导意义。
