A novel compound of antimycin family, JBIR-06 (1), was isolated from Streptomyces sp. ML55. The structure of 1 was established as a twelve-membered macrocyclic skeleton with a 3-(formylamino)-2-hydroxybenzamide based on the spectroscopic data. Compound 1 inhibited the expression of GRP78 induced by 2-deoxyglucose at the IC 50 value of 250 nM.Keywords antimycin, JBIR-06, molecular chaperone, GRP78, Streptomyces sp. GRP78, which is well-known as a molecular chaperone in the endoplasmic reticulum (ER), also plays an important role as a survival factor in solid tumors, due to its acquisition of a resistant mechanism against both chemotherapy and hypoglycemic stress [1]. Thus, specific down-regulators of GRP78 transcription can reasonably be expected to become promising drugs in cancer chemotherapy [2]. In the course of our screening program for down-regulators of GRP78/Bip molecular chaperone expression, we isolated versipelostatin [3], prunustatin A [4, 5], JBIR-04, -05 [6] and SW-163A [6]. Further screening resulted in the isolation of a novel inhibitor of GRP78 expression, designated as JBIR-06 (1, Fig. 1), a new member of antimycin [7] family from mycelium of Streptomyces sp. ML55 [8]. In this paper, we report the isolation, structure elucidation, and brief biological activities of 1.The Streptomyces sp. ML55 was cultured at 27°C for 5 days in 500-ml Erlenmeyer flasks containing a medium consisting of 2.0% glycerin (Nacalai Tesque), 1.0% molasses (Dai-Nippon Meiji Sugar), 0.5% casein (KANTO CHEMICAL), 0.1% polypepton (NIHON PHARMACEUTICAL), 0.4% CaCO 3 (KOZAKAI PHARMACEUTICAL) (pH 7.2 before sterilization). The mycelium from the culture broth (2.0 liters) was extracted with Me 2 CO (400 ml). After concentrated in vacuo, the residue was extracted with EtOAc for two times. The organic layer was dried over Na 2 SO 4 , and concentrated in vacuo. The dried residue was applied to normal-phase MPLC (Purif-Pack SI-60, Moritex) and developed with a

In the course of our screening program for novel metabolites from tunicate-derived fungi, novel sesquiterpenoids, named JBIR-27 (1) and -28 (2), together with known sporogen-AO1 and phomenone, were isolated from the culture broth of Penicillium sp. SS080624SCf1. The structures of 1 and 2 were determined to be eremophilane analogs on the basis of extensive NMR and MS analyses. Sporogen-AO1, phomenone and 2 showed cytotoxicity against human cervical carcinoma cell line HeLa at IC 50 values of 8.3, 19 and 92 mM, respectively, whereas 1 was inactive at a concentration of 80 mM. Keywords: cytotoxicity; JBIR-27; JBIR-28; Penicillium sp.; terpenoid; tunicate INTRODUCTION Many bioactive substances have been isolated from marine organisms, such as marine microorganisms, phytoplankton, algae, sponges and tunicates. Moreover, marine microorganisms have been studied as the important resources for new biologically active metabolites. 1 Especially, marine-derived fungi are emerging as an attractive source for discovering new bioactive compounds. 2 Indeed, cytotoxic metabolites, such as diketopiperazine alkaloids, 3 trichodermatides 4 and carbonarones, 5 have been isolated from metabolites of marine-derived fungi. Tunicates are a rich source of unique and biologically active metabolites. 1 However, there have been few reports of compounds isolated from tunicate-derived fungi. 6,7 Therefore, we attempted to isolate fungi from a tunicate, Didemnum molle, and obtain secondary metabolites from the fungal culture broths.In the course of chemical screening for novel compounds from the metabolites of tunicate-derived fungi, we isolated two novel sesquiterpenoid compounds, designated as JBIR-27 (1) and -28 (2), from the culture broth of Penicillium sp. SS080624SCf1 (Figure 1). In addition, we also isolated known derivatives, sporogen-AO1 8 and phomenone 9 (Figure 1). This paper describes the fermentation, isolation and brief biological activity of 1, 2, sporogen-AO1 and phomenone, in addition to the taxonomy of the producing microorganism. The structure elucidation of 1 and 2 is also reported.

Screening for anti-influenza virus activity in compounds isolated from Streptomyces sp. RI18, which was isolated using the membrane filter method, uncovered a novel compound, JBIR-68 (1), which contains a unique skeleton. Its structure was established by extensive NMR and MS analyses. In addition, 1 was synthesized to confirm the configuration of its sugar moiety. Compound 1 inhibited influenza virus growth in plaque assays.