Tawfike Ahmed, Attia Eman Zekry, Desoukey Samar Yehia, Hajjar Dina, Makki Arwa A, Schupp Peter J, Edrada-Ebel RuAngelie, Abdelmohsen Usama Ramadan
Computational and Analytical Science Department, Rothamsted Research, AL5 2JQ, Harpenden, UK.
Department of Pharmacognosy, Faculty of Pharmacy, Helwan University, Cairo, 11795, Egypt.
AMB Express. 2019 Jan 24;9(1):12. doi: 10.1186/s13568-018-0730-0.
Several approaches have been dedicated to activate the cryptic gene clusters in the genomes of actinomycetes for the targeted discovery of new fascinating biomedical lead structures. In the current study, N-acetylglucosamine was used to maximize the chemical diversity of sponge-derived actinomycete Actinokineospora spheciospongiae sp. nov. HR-ESI-MS was employed for dereplication study and orthogonal partial least square-discriminant analysis was applied to evaluate the HR-ESI-MS data of the different fractions. As a result, two new fridamycins H (1) and I (2), along with three known compounds actinosporin C (3), D (4), and G (5) were isolated from the solid culture of sponge-associated actinomycete Actinokineospora spheciospongiae sp. nov., elicited with N-acetylglucosamine. Characterization of the isolated compounds was pursued using mass spectrometry and NMR spectral data. Fridamycin H (1) exhibited significant growth inhibitory activity towards Trypanosoma brucei strain TC221. These results highlight the potential of elicitation in sponge-associated actinomycetes as an effective strategy for the discovery of new anti-infective natural products.
为了有针对性地发现新的、引人入胜的生物医学先导结构，人们采用了多种方法来激活放线菌基因组中的隐性基因簇。在本研究中，使用N-乙酰葡糖胺来最大化海绵源放线菌球形动孢菌新种Actinokineospora spheciospongiae的化学多样性。采用高分辨电喷雾电离质谱（HR-ESI-MS）进行去重复研究，并应用正交偏最小二乘判别分析来评估不同馏分的HR-ESI-MS数据。结果，从用N-乙酰葡糖胺诱导的海绵相关放线菌球形动孢菌新种的固体培养物中分离出两种新的弗氏霉素H（1）和I（2），以及三种已知化合物放线菌素C（3）、D（4）和G（5）。利用质谱和核磁共振光谱数据对分离出的化合物进行了表征。弗氏霉素H（1）对布氏锥虫菌株TC221表现出显著的生长抑制活性。这些结果突出了在海绵相关放线菌中诱导作为发现新的抗感染天然产物的有效策略的潜力。
