In this work, we report the isolation and detailed functional characterization for the new non-ribosomally synthesized antibiotic 5812-A/C, which was derived from metabolites of Streptomyces roseoflavus INA-Ac-5812. According to its chemical structure, the studied 5812-A/C preliminary is composed of a cyclic peptide part covalently bounded with an arabinose residue. N-terminal amino acid sequencing of the native peptide has identified its partial structure of Leu-Asp-Gly-Ser-Gly and consisting of a Tyr residue that is supposed to have a two-component peptide nature for the molecule studied. However, the structural analysis of the antibiotic complex derived from S. roseoflavus INA-Ac-5812 is still ongoing. The mechanism of action of 5812-A/C was assessed in comparison with its most related analog, the lipopeptide antibiotic daptomycin, given the presence in both antimicrobials of an L-kynurenine amino acid residue. The inhibitory activity of 5812-A/C against Gram-positive bacteria including methicillin-resistant strain of Staphylococcus aureus was similar to daptomycin. The mechanism of action of 5812-A/C was associated with the disruption of membrane integrity, which differs in comparison with daptomycin and is most similar to the antimicrobial membrane-disturbing peptides. However, 5812-A/C demonstrated a calcium-dependent mode of action. In addition, unlike daptomycin, 5812-A/C was able to penetrate mature biofilms and inhibit the metabolic activity of embedded S. aureus cells. At the same time, 5812-A/C has no hemolytic activity toward erythrocyte, but possessed weak cytotoxic activity represented by heterochromatin condensation in human buccal epithelium cells. The biological properties of the peptide 5812-A/C suggest its classification as a calcium-dependent antibiotic effective against a wide spectrum of Gram-positive pathogenic bacteria.

在这项工作中，我们报告了新的非核糖体合成抗生素5812-A / C的分离和详细的功能表征，该抗生素衍生自 玫瑰黄链霉菌INA-Ac-5812。根据其化学结构，所研究的5812-A / C初级化合物由与阿拉伯糖残基共价结合的环状肽部分组成。天然肽的N端氨基酸测序已确定其Leu-Asp-Gly-Ser-Gly的部分结构，并由一个Tyr残基组成，该残基被认为对所研究的分子具有双组分肽性质。但是，抗生素复合物的结构分析来源于玫瑰黄酮INA-Ac-5812仍在进行中。考虑到5812-A / C的作用机理与最相关的类似物脂肽抗生素达托霉素相比，两种药物均存在大号-犬尿氨酸氨基酸残基。5812-A / C对革兰氏阳性细菌（包括耐甲氧西林菌株）的抑制活性金黄色葡萄球菌与达托霉素相似。5812-A / C的作用机制与膜完整性的破坏有关，与达托霉素相比有所不同，并且与抗微生物膜干扰肽最相似。但是，5812-A / C表现出钙依赖性的作用方式。此外，与达托霉素不同，5812-A / C能够穿透成熟的生物膜并抑制包埋的代谢活性。金黄色葡萄球菌细胞。同时，5812-A / C对红细胞没有溶血活性，但在人颊上皮细胞中异染色质凝结表现出弱的细胞毒活性。多肽5812-A / C的生物学特性表明，其分类为对多种革兰氏阳性致病菌均有效的钙依赖性抗生素。