Lumazine Peptides from the Marine-Derived Fungus Aspergillus terreus

Abstract

2012년 제주도에서 채집된 해양 퇴적물로부터 분리된 균주인 Aspergillus terreus의 배양물을 추출 후, 정제하여 2개의 신규 peptides와 19개의 기지 물질들을 분리하였다. 다양한 분광학적 기법과 화학적 분석법을 이용하여 신규 peptides의 구조는 1-methyllumazine-6-carboxylic acid, 아미노산, 그리고 anthranilic acid methyl ester가 선형의 아미드 결합으로 연결된 것임을 규명하였다. 신규 물질들의 입체 구조는 Advanced Marfeys method를 이용하여 각각 L-Threonine과 L-Serine임을 결정하였다. 다양한 생리 활성을 검정해본 결과, 신규 물질은 인간 골수 중간엽 줄기세포의 adipogenesis model에서 인슐린 감수성을 개선시키는 약리 효과를 가지고 있음을 확인하였고, 그 효과는 glibenclamide보다 약하고 aspirin보다 강하게 나타났다.

The marine-derived fungi are the prolific source of the novel compounds among the natural products. A number of fungal strains were isolated from the marine-related samples, and evaluated by combined spectroscopic analyses of their metabolites. A marine-derived fungal strain, Aspergillus terreus, was isolated from the off-shore sediment in Jeju, Korea. It was cultivated for 6 weeks in YMM static condition, and extracted with organic solvent. The organic extracts were separated with various chromatographic methods and analyzed with combined spectroscopic methods. In total, 2 new compounds and 17 known compounds were structurally determined and identified as 3 peptides, 1 pyridione containing compound, 2 alkaloids, 5 terpenoids, 7 amino acid derived compounds, 1 polyene compound. The new compounds were structurally elucidated to be linear assemblies of 1-methyllumazine-6-carboxylic acid, an amino acid residue and anthranilic acid methyl ester connected by peptide bonds. The absolute stereochemistry were determined by advanced Marfeys analysis. The new compounds have a pharmacological activity to improve the insulin sensitivity, which was evaluated in the adipogenesis model in human bone marrow mesenchymal stem cells.