PDF(Pubmed)
Abstract：
Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey\'s analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.
摘要：
对未充分开发的放线菌类群的次生代谢进行生物勘探是发现新化学的多产途径。在这项工作中,我们报告隔离，结构阐明，以及纤维素酶A和B（1和2）的生物活性筛选，从巨藻相关的CellulosimiumfunkeiCT-R177的培养物中获得的两种新型线性肽。这种微生物的宿主，绿藻门，被收集在葡萄牙北部海岸，在一项针对其相关放线菌群落的生物勘探研究范围内，分离菌株CT-R177，分类识别，并筛选抗菌和抗癌化合物的生产。使用LC-HRMS（/MS）分析对该菌株的粗提物进行扩增，揭示了一种推定的新型天然产物，纤维素酶A(1)，在质谱引导的分馏后分离。一个额外的模拟，在色谱过程中获得了纤维素酰胺B（2），并进行了化学表征。新型线性肽的化学结构，包括它们的绝对配置，使用HRMS的组合进行了阐述，1D/2DNMR光谱，和Marfey的分析。对纤维素酰胺A（1）进行了一系列生物活性筛选，但没有观察到显著的生物活性。纤维素酰胺代表放线菌属的第一个天然产物家族，不仅展示了探索较少的分类单元的潜力，还展示了与宿主相关的海洋菌株对新化学发现的潜力。
