Biomedicinal Information Research Center, Japan Biological Informatics Consortium, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
J Nat Prod. 2010 Feb 26;73(2):208-12. doi: 10.1021/np900747t.
In the course of our screening program for isoprenoids of marine actinobacterial origin, 523 actinobacterial strains were isolated from marine samples. Actinobacteria usually use the 2-C-methyl-d-erythritol 4-phosphate pathway for the production of primary metabolites, but some have been reported to use the mevalonate (MVA) pathway for the production of isoprenoids as secondary metabolites. 3-Hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) is a key enzyme and plays an important role in the MVA pathway. Therefore, we screened strains possessing the HMGR gene from the 523 strains mentioned above and also investigated isoprenoid compounds from cultures of strains possessing HMGR genes. As a result, Streptomyces sp. SpC080624SC-11 isolated from a marine sponge, Cinachyra sp., was shown to possess the HMGR gene and produce novel isoprenoids, JBIR-46 (1), -47 (2), and -48 (3). On the basis of extensive NMR and MS analyses, the structures of 1-3 were determined to be phenazine derivatives harboring dimethylallyl moieties. Furthermore, the isoprene units of 2 and 3 were confirmed to be synthesized via the MVA pathway in a feeding experiment using [1-(13)C]acetate.
在我们对海洋放线菌来源的异戊烯类化合物的筛选计划中，从海洋样本中分离出了 523 株放线菌。放线菌通常使用 2-C-甲基-D-赤藓醇 4-磷酸途径来生产初级代谢物，但也有报道称，一些放线菌使用甲羟戊酸（MVA）途径来生产异戊烯类化合物作为次级代谢物。3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMGR）是一种关键酶，在 MVA 途径中发挥重要作用。因此，我们从上述 523 株菌中筛选出了具有 HMGR 基因的菌株，并对具有 HMGR 基因的菌株的培养物中的异戊烯类化合物进行了研究。结果表明，从海绵 Cinachyra sp.中分离到的海洋放线菌 Streptomyces sp. SpC080624SC-11 具有 HMGR 基因，并产生了新型异戊烯类化合物 JBIR-46（1）、-47（2）和-48（3）。通过广泛的 NMR 和 MS 分析，确定了 1-3 的结构为含有二甲基烯丙基部分的吩嗪衍生物。此外，通过使用 [1-(13)C]乙酸进行的喂食实验，证实了 2 和 3 的异戊二烯单元是通过 MVA 途径合成的。
