Xia Runjie, Xie Hannuo, Solorzano Mahmud Allyson M, Bertin Matthew J
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, United States.
St. Vincent-St. Mary High School, Akron, Ohio 44303, United States.
J Nat Prod. 2025 Aug 22;88(8):1950-1957. doi: 10.1021/acs.jnatprod.5c00619. Epub 2025 Aug 3.
Cyanobacterial blooms are a significant environmental concern due to their production of toxic metabolites with potential impacts on ecosystem and human health. Microcystin-LR and microcystin congeners are a major concern with respect to human exposure and intoxication, but there are hundreds of characterized cyanobacterial peptides and metabolites that are of interest for their environmental impact in a variety of classes such as cyanopeptolins/micropeptins, microviridins, microginins, and anabaenopeptins. In this study, we report the isolation and characterization of new micropeptins (), a new ferintoic acid () a new microginin (), and three new microviridins () from a cyanobacterial bloom sample. The new micropeptins, in particular, exhibited unprecedented modifications in their amino acid composition and configuration, which differentiate them from previously known variants. Certain alterations significantly influenced their biological activity with respect to chymotrypsin inhibition and human neutrophil elastase inhibition, highlighting the potential ecological and biomedical relevance of these compounds. We report d-amino acid incorporation into the micropeptins for the first time providing new insights into the chemical diversity of cyanobacterial natural products. These results have important implications for understanding biosynthetic flexibility, the development of bioactive agents for therapeutic applications, and highlight the need for reference materials for mass spectrometry-based metabolite annotation.
蓝藻水华是一个重大的环境问题，因为它们会产生有毒代谢产物，对生态系统和人类健康有潜在影响。微囊藻毒素-LR和微囊藻毒素同系物是人类接触和中毒的主要关注点，但还有数百种已鉴定的蓝藻肽和代谢产物，因其在蓝藻肽/微肽、微绿肽、微精氨酸和鱼腥藻肽等各类物质中的环境影响而备受关注。在本研究中，我们报告了从蓝藻水华样本中分离并鉴定出新型微肽（）、新型铁托酸（）、新型微精氨酸（）以及三种新型微绿肽（）。特别是新型微肽，其氨基酸组成和构型呈现出前所未有的修饰，这使其有别于先前已知的变体。某些改变显著影响了它们对胰凝乳蛋白酶抑制和人中性粒细胞弹性蛋白酶抑制的生物活性，凸显了这些化合物潜在的生态和生物医学相关性。我们首次报道了微肽中掺入了d-氨基酸，这为蓝藻天然产物的化学多样性提供了新的见解。这些结果对于理解生物合成的灵活性、开发用于治疗应用的生物活性剂具有重要意义，并强调了基于质谱的代谢物注释参考材料的必要性。
