Davis Lydia J, Krunić Aleksej, Alexander Kelsey, Khin Manead, Wood Jared S, Earp Cody, Rangel-Grimaldo Manuel, Eustáquio Alessandra S, Burdette Joanna E, Williamson R Thomas, Oberlies Nicholas H, Orjala Jimmy
Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois 60612, United States.
Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28409, United States.
J Nat Prod. 2025 Mar 28;88(3):732-746. doi: 10.1021/acs.jnatprod.4c01445. Epub 2025 Feb 20.
Menominin A () and B (), two cyclodepsipeptides containing a 3,8-dihydroxy-2-methyltetradecanoic acid residue, were isolated from the freshwater sponge-associated cyanobacterium, sp. UIC 10607, using bioactivity-guided and spectroscopic approaches. The planar structures of and were established using HRESIMS and one- and two-dimensional NMR experiments. Comparative genomic analysis revealed unique differences in the putative menominin biosynthetic gene cluster compared to that of the closely related cyanobacterial cyclic lipodepsipeptide, hapalosin, assisting in structure elucidation and highlighting the structural diversity of this class of compounds. Configuration assignments were determined using a combination of -based configuration analysis, chiral HPLC, modified Mosher's ester analysis, and DFT calculations. Menominin A and B demonstrate antiproliferative bioactivity against the high-grade serous ovarian cancer cell line OVCAR3 (IC = 3.1 () and 2.4 μM ()). Menominin A and B are the first reported secondary metabolites from a freshwater sponge-associated cyanobacterium, underscoring the potential of freshwater sponges as a microbial culture source in natural product discovery.
从与淡水海绵相关的蓝藻菌Menomirabilis sp. UIC 10607中，采用生物活性导向和光谱学方法分离出了含有3,8-二羟基-2-甲基十四烷酸残基的环缩肽类化合物米诺米宁A（）和B（）。利用高分辨电喷雾电离质谱（HRESIMS）以及一维和二维核磁共振实验确定了米诺米宁A和B的平面结构。比较基因组分析显示，与密切相关的蓝藻环脂缩肽哈帕洛辛相比，推测的米诺米宁生物合成基因簇存在独特差异，这有助于结构解析并突出了这类化合物的结构多样性。使用基于量子化学计算的构型分析、手性高效液相色谱、改良的莫舍尔酯分析和密度泛函理论（DFT）计算相结合的方法确定了构型归属。米诺米宁A和B对高级别浆液性卵巢癌细胞系OVCAR3表现出抗增殖生物活性（IC50分别为3.1（）和2.4 μM（））。米诺米宁A和B是首次报道的来自与淡水海绵相关蓝藻菌的次生代谢产物，强调了淡水海绵作为天然产物发现中微生物培养来源的潜力。
