Ocean College, Zhejiang University, Zhoushan 316021, China.
Ocean College, Zhejiang University, Zhoushan 316021, China; School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
Mar Genomics. 2023 Aug;70:101033. doi: 10.1016/j.margen.2023.101033. Epub 2023 Apr 27.
Streptomyces sp. HNA39 is a promising candidate for the production of antineoplastic metabolites screened from a collection of 448 actinomycetes derived from coastal sediments. The complete genome sequence of HNA39 comprises a 7,351,753-bp linear chromosome with a GC content of 71.94%. Whole genome analysis reveals the presence of 29 putative biosynthetic gene clusters (BGCs) encoding secondary metabolites. Among them, a type I PKS BGC shows an 82% similarity with the cyclizidine (CLD) BGC identified from Streptomyces NCIB 11649. LC-MS profiles further supported the production of new CLD congeners. Bafilomycins were also found produced in abundance, corresponding to another type I PKS BGC highly homologous to that of bafilomycin B1 from S. lohii. CLDs are indolizidine alkaloids consisting a fused five- and six-membered ring system with an intriguing cyclopropane terminal linked by a trans-dienic chain. The cyclization mechanism of the cylopropyl ring, one of its pharmacophores, is still unknown. Genome sequencing of the new CLD producer and subsequent comparative analysis of their gene clusters would further our understanding of the chemistry behind cyclopropane formation.
链霉菌 HNA39 是一种很有前途的候选菌株，它可以从取自沿海沉积物的 448 株放线菌中筛选出抗肿瘤代谢产物。HNA39 的全基因组序列由一条 7,351,753bp 的线性染色体组成，GC 含量为 71.94%。全基因组分析显示存在 29 个可能的生物合成基因簇（BGCs），编码次级代谢产物。其中，一个 I 型 PKS BGC 与从链霉菌 NCIB 11649 中鉴定出的环二肽（CLD）BGC 具有 82%的相似性。LC-MS 图谱进一步支持了新的 CLD 同系物的产生。丰度也发现了巴佛洛霉素的产生，这对应于另一个与 S. lohii 中的巴佛洛霉素 B1 高度同源的 I 型 PKS BGC。CLD 是吲哚里西啶生物碱，由一个融合的五元环和六元环系统组成，具有一个通过反式二烯链连接的有趣的环丙烷末端。其药效团之一的环丙烷环的环化机制尚不清楚。新型 CLD 产生菌的基因组测序以及对其基因簇的后续比较分析将有助于我们了解环丙烷形成背后的化学原理。
