Therefore, we investigated whether these strains possessed the 3-hydroxyl-3-methylglutaryl coenzyme A reductase (hmgr) gene, which indicates the presence of the mevalonate pathway. As a result, six strains belonging to the genera Streptomyces (SpC080624SC-11, SpA080624GE-02, and Sp080513GE-23), Nocardia (Sp080513SC-18), and Micromonospora (Se080624GE-07 and SpC080624GE-05) were found to possess the hmgr gene, and these genes were highly similar to hmgr genes in isoprenoid biosynthetic gene clusters. Among the six strains, selleck chemicals llc the two strains
SpC080624SC-11 and SpA080624GE-02 produced the novel isoprenoids, JBIR-46, -47, and -48, which consisted of phenazine chromophores, and Sp080513GE-23 produced a known isoprenoid, fumaquinone. Furthermore, these compounds showed cytotoxic activity against human acute myelogenous leukemia HL-60 cells. Isoprenoids are the largest family of compounds found in nature. With over 30 000 known examples, isoprenoids include industrially useful compounds such as flavors, antibiotics, and plant hormones BMN 673 nmr (Bohlmann & Keeling, 2008). Isoprenoids are composed of units of isopentenyl diphosphate (IPP), which can be synthesized by two independent pathways: the mevalonate pathway and/or the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway (Kuzuyama & Seto, 2003). All Actinobacteria, including Streptomycetes,
use only the MEP pathway for the formation of IPP as a primary metabolite. On the other hand, some Actinobacteria strains possessing the MEP pathway have been reported to use the mevalonate DOK2 pathway for the production of isoprenoids
as secondary metabolites. These strains include Kitasatospora griseola (terpentecin producer; Isshiki et al., 1986), Actinoplanes sp. A40644 (BE-40644 producer; Seto et al., 1998), Streptomyces sp. CL190 (naphterpin A producer; Shin-ya et al., 1990; Takahashi et al., 1999; Takagi et al., 2000), Streptomyces sp. KO-3988 (furaquinocin A producer; Funayama et al., 1990), Streptomyces griseolosporeus MF730-N6 (terpentecin, Dairi et al., 2000; Hamano et al., 2001), Chainia rubra (napyradiomycin A producer; Shiomi et al., 1986), and Streptomyces cinnamonensis (furanonaphthoquinone I and endophenazine A producer; Bringmann et al., 2007). Because these isoprenoids show interesting biological activities, including antitumor, antibacterial, and antioxidative properties, novel isoprenoids produced by Actinobacteria are expected to be promising candidates for drug discovery. In addition, it has been reported that Actinobacteria possessing a key enzyme gene, the 3-hydroxyl-3-methylglutaryl coenzyme A reductase (hmgr) gene, in the mevalonate pathway produce terpenoids (Kuzuyama et al., 2002). Therefore, we screened isoprenoids from Actinobacteria possessing the hmgr gene.