Isolation of 3'-methyl-5'-pentyl-furylarylic Acid from Marine-derived Alteromonas sp.

Abstract

천연물이란 식물, 토양미생물, 해양미생물 등 생명체로부터 얻을수 있는 대사산물을 뜻한다. 천연물 연구는 화합물이 갖고 있는 화학 구조의 다양성 및 유용 생리활성에 기반한 신약개발에 있어 중요한 의미를 갖는다. 지구표면적의 70%는 바다이고 생명체 중 80%가 서식하고 있지만, 해양생물은 육상에서의 연구에 비해 역사가 짧으며, 특히 해양미생물은 배양 및 분리의 어려움으로 유전 자원이 충분히 이용되지 못하고 있다. 최근 해양미생물의 풍부한 이차대사산물은 생리활성물질 원천으로 각광받으면서, 이의 특이한 화학구조와 약리활성에 대해 많은 연구가 이루어 지고 있다. 본 연구에서는 식물 종인 미리스티카 프라그란스 (Myristica fragrans)에서 발견된 3'-methyl-5'-pentyl-furylarylic acid를 최초로 해양미생물 알테로모나스균주 (Alteromonas sp.)에서 분리하였다. 알테로모나스균주는 해안 또는 외해 (open ocean)에서 서식하며, 주로 해면 (marine sponge) 에서 발견되는데, 이의 이차대사산물에 대해 현재 많은 연구가 이루어지고 있다. 알테로모나스균주의 이차대사를 통해 생성된 3'-methyl-5'-pentyl-furylarylic acid는 HPLC를 이용하여 분리하였고, 화합물의 구조를 확인하기 위하여 NMR, MS 및 UV 스펙트럼 등 방법을 수행 하였다. 최종적으로 3'-methyl-5'-pentyl-furylarylic acid 는 식물 종인 미리스티카 프라그란스에서 보다 해양미생물 알테로모나스균주에서 약 136배 더 많은양이 생산되었음이 확인되었다. 이러한 결과는, 높은 생산성에 기반한 해양미생물 유래의 새로운 후보약물 개발에 긍정적 가능성을 제시한다. ;Natural product derived from naturally living organism is a chemical compounds or substances. Natural product research has an extremely important significance for organic chemistry, study for diversity of chemical structure, development of bioactive compounds and new drug discovery. The main source of natural products includes plants, soil microorganisms and marine microorganisms. In this thesis, the production of 3'-methyl-5'-pentyl-furylarylic acid from marine-derived bacteria Alteromonas sp. SNA020 was verified. 3'-methyl-5'-pentyl-furylarylic acid is a naturally produced acid, which is firstly found and isolated from a plant named Myristica fragrans in 2010. Alteromonas sp. is a marine microorganism and a genus of proteobacteria, which is derived from the open ocean or the coast. It is a Gram-negative bacteria and belongs to the γ-subclass of proteobacteria. The genus Alteromonas was generally derived from marine sponges. Several secondary metabolites of genus Alteromonas have been explored, including sulfur-containing secondary metabolites, tetracyclic alkaloid alteramide and ubiquinone. During study on the secondary metabolites of the Alteromonas sp., the 3'-methyl-5'-pentyl-furylarylic acid was found. Further, we utilized HPLC to successfully isolate this acid from diverse materials that were produced from Alteromonas sp. Moreover, various analyses for the structural characterization were also carried out, including NMR, MS and UV spectra. The chemical structure of 3'-methyl-5'-pentyl-furylarylic acid was also successfully verified. As far as we know, this is the first study on the isolation of 3'-methyl-5'-pentyl-furylarylic acid from marine-derived Alteromonas sp. The amount of 3'-methyl-5'-pentyl-furylarylic acid obtained from Alteromonas sp. SNA020 is nearly 136 times higher than Myristica fragrans. The high productivity of 3'-methyl-5'-pentyl-furylarylic acid makes it attractive to explore the possibility of new compounds discovery from marine-derived bacteria.