Thiomarinol, an antimicrobial antibiotic, was isolated from the culture broth of a marine bacterium, Alteromonas rava sp. nov. SANK73390. Its structure was deduced as a hybrid composed of a pseudomonic acid analogue and holothin by NMRspectral analysis and chemical degradation. Antimicrobial activity against Gram-positive and Gram-negative bacteria of thiomarinol was stronger than both of pseudomonic acids and pyrrothine antibiotics.

New inositol-l,4,5-trisphosphate (InsP3) agonists, adenophostins A(l) and B(2), were isolated from the culture broth of Penicillium brevicompactum SANK1 1991 and SANK12177. Its structures were related to adenine nucleotides. The agonistic activity of adenophostins A or B for binding to the InsP3 receptor was higher than InsP3 itself. It is now well knownthat calcium ions play an important role in manycellular processes, including neural activity, muscle contraction, various secretion reactions and cellular growth and differentiation. Accordingly, the increase of intracellular calcium concentration is important to the operation of these processes, and compounds with the ability to control this release clearly have great potential for use in therapy. Inositol-l,4,5-trisphosphate (InsP3) is a second messenger in a wide variety of cell types, and has an important role on the release of calcium ions from internal stores to the cytosol1}.In our search for activities inhibiting the binding of [3H]-InsP3 to rat cerebellar membranes, we found adenophostins A and B, which were isolated from the cultured broth of Penicillium brevicompactum SANK11991 and SANK12177. Adenophostins A and B are potent InsP3 receptor agonists, which bind to the InsP3 receptor, and induce Ca2+ release from InsP3 sensitive calcium stores. In this paper, we report the taxonomic studies of strain SANK1 1991 and SANK12177, the fermentation of the producing organism and the isolation, physico-chemical and biological properties of adenophostins A and B.Structures and biological activity for InsP3 receptor of adenophostins in detail will be published elsewhere. Materials and Methods Taxonomic StudiesThe adenophostins-producing strains were identified by using technique as described by Pitt2). The colors are indicated herein according to Kornerup and Wanscher3). Inhibitory Activity on [3H]-InsP3Binding to InsP3 Receptor The InsP3 receptor was purified form rat cerebellum using heparin-agarose and concanavalinASepharose4).Binding of [3H]-InsP3 to the purified InsP3 receptor was determined by using polyethyleneglycol (PEG) precipitation method5). Samples were incubated in 250/A of 1 jug of the purified receptor, 50mMofTris-HCl (pH 8.0), 1 him ofEDTA, 1 mMof2-mercaptoethanol and 10nM of [3H]-InsP3 at 4°C. After 5minutes, the sample was mixed with 5//I of 5% (w/v) y-grobulin and 250//I of 30% PEG

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Three metabolites were isolated from the culture broth of an actinomycete strain identified as Streptomycesplatensis SANK601 91 , that induce the production of colony-stimulating factors (CSFs) by stromal cell line KM-102at ED50concentrations from 40 to 200 ng/ml. The compounds induced quantities of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) comparable to those induced by interleukin-1 , a strong CSFinducer. These metabolites were called leustroducsins (A, B and C) and were later found to be structurally related to phoslactomycins. This is the first report of CSFinducing activity by members of the phoslactomycin class. 1503Recent studies have demonstrated the application of colony-stimulating factors (CSFs) in clinical use1}. These substances have been used to recover the peripheral blood leukocytes in leukopenia patients caused by cancer-chemotherapy, radiotherapy and bone marrowtransplantation. WhenCSFs were administered to patients, restorations ofleukocyte counts occurred. However,the in vivo role ofendogenous CSFs is not precisely understood. In particular, little is known about the regulatory mechanism for CSF production or about the relationship between normal blood cell production and endogenous CSFs. It is well knownthat bone marrow stromal cells play an important role in hematopoiesis. Regulation of CSF production by bone marrow stromal cells may be one of the key elements responsible for the control of hematopoiesis in vivo2). Therefore, substances that affect the regulation of CSF production by stromal cells are of potential interest, so we worked to develop screening methods for CSF inducers.In the previous paper3), we described the development of a new screening method for CSF inducers using human bone marrow stromal cell line KM-102. Using this screening method, one strain of actinomycetes, Streptomyces platensis SANK60191, was found to produce novel microbial metabolites that we provisionally namedleustroducsins. Structure determination studies revealed that they are congeners of phoslactomycins. In this paper we report the taxonomy of the producing organism, and also describe the fermentation and biological properties of leustroducsins (LSNs), A, B and C (Fig. 1). The isolation, physicochemical properties and structural elucidation of the metabolites are reported in the accompanying paper4).

A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK17777. The molecular formula, physicochemical properties, NMRspectroscopic analysis and X-ray crystallographic analysis revealed that this compoundwas a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACATactivity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7pu. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75mg/kg.