Guerrero Garzón Jaime Felipe, Zehl Martin, Schneider Olha, Marquez Inmaculada Tocino, Rückert-Reed Christian, Kalinowski Jörn, Zotchev Sergey B
Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Vienna, 1090, Austria.
Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, 1090, Austria.
Sci Rep. 2025 Sep 1;15(1):32142. doi: 10.1038/s41598-025-17585-y.
Streptomyces bambergiensis AC-800 is known as a producer of moenomycin family antibiotics active against gram-positive bacteria. Complete genome sequencing of S. bambergiensis revealed 3 replicons represented by the linear chromosome (7,652,101 bp) and two linear plasmids, pSB1 (418,507 bp) and pSB2 (81,486 bp). Analysis of the chromosome for the presence of secondary metabolite biosynthesis gene clusters (BGCs) revealed 25 BGCs, while other 4 were located on the linear plasmid pSB1. The bioinformatics-based analysis of the moenomycin BGC provided new insights into its biosynthesis. The largest reported polyketide synthase gene cluster spanning over 190 kb was identified on the pSB1 plasmid, with its putative product likely to be represented by a 67-membered glycosylated macrolide related to stambomycins. Co-cultivation of S. bambergiensis AC-800 with a strain of Rhodococcus isolated from a fresh-water bryozoan induced production of a red pigment tentatively identified as fibrostatin. CRISPR-BEST-assisted inactivation of the only PKSIII-encoding gene abolished the production of fibrostatin, allowing the identification of the previously unreported fibrostatin BGC. Subsequent secondary metabolomics of S. bambergiensis cultivated in different media revealed production of both known and presumably novel compounds. This study sets a stage for further investigation of this strain by means of genome mining that may result in the discovery of novel bioactive natural products.
班贝格链霉菌AC-800是一种已知的莫能菌素家族抗生素的生产者，该抗生素对革兰氏阳性菌具有活性。班贝格链霉菌的全基因组测序揭示了3个复制子，分别由线性染色体（7,652,101 bp）和两个线性质粒pSB1（418,507 bp）及pSB2（81,486 bp）代表。对染色体上次生代谢物生物合成基因簇（BGCs）的存在情况进行分析，发现了25个BGCs，而另外4个位于线性质粒pSB1上。基于生物信息学对莫能菌素BGC的分析为其生物合成提供了新的见解。在pSB1质粒上鉴定出了报道中最大的聚酮合酶基因簇，其跨度超过190 kb，其推定产物可能是一种与斯坦波霉素相关的67元糖基化大环内酯。班贝格链霉菌AC-800与从淡水苔藓虫分离出的一株红球菌共培养，诱导产生了一种暂定为纤维抑素的红色色素。CRISPR-BEST辅助失活唯一的编码PKSIII的基因消除了纤维抑素的产生，从而鉴定出了之前未报道的纤维抑素BGC。随后对在不同培养基中培养的班贝格链霉菌进行次生代谢组学分析，揭示了已知化合物和可能的新化合物的产生。这项研究为通过基因组挖掘进一步研究该菌株奠定了基础，这可能会导致发现新型生物活性天然产物。
