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A novel Gram-stain-positive actinomycete, designated MB-PO13(T), was isolated from a tunicate (Molgula manhattensis) collected in Tokyo Bay, Japan, and its taxonomic position was studied by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain MB-PO13(T) was closely related to Streptomyces graminisoli JR-12(T) (99.72% 16S rRNA gene sequence similarity) and Streptomyces shenzhenensis 172115(T) (99.23%). The strain contained LL-diaminopimelic acid in the whole-cell hydrolysate. The predominant menaquinones were MK-9(H8) and MK-9(H6) and the major fatty acids were anteiso-C15:0, iso-C16:0, iso-C14:0 and C16:0. These data supported the affiliation of the novel strain to the genus Streptomyces. Meanwhile, results of DNA-DNA hybridization and physiological and biochemical tests indicated that strain MB-PO13(T) was distinguished from known Streptomyces type strains. Therefore, strain MB-PO13(T) represents a novel species of the genus Streptomyces for which the name Streptomyces hyaluromycini sp. nov. is proposed; the type strain is MB-PO13(T) (=NBRC 110483(T) =DSM 100105(T)).

Diketopiperazines, inhibitors of sterol O -acyltransferase, produced by a marine-derived Nocardiopsis sp. KM2-16

Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated production and degradation of hyaluronan (HA), a major component of extracellular matrix involved in the malignant phenotype of cancer. In particular, increased hyaluronidase (HYAL) activity plays a critical role in cancer progression, at least in part, by producing low-molecular-weight- (LMW-) HA or small fragments of HA, suggesting HYAL as a target for cancer treatment. Hyaluromycin, a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derivedStreptomyces hyaluromycinias a HYAL inhibitor. We investigated the antitumor effects of hyaluromycin in PDAC cells. We examined the effects of hyaluromycin on the proliferation and migration of PDAC cells. To elucidate the mechanisms underlying the effect of hyaluromycin on PDAC cells, we examined the concentration of LMW-HA in the conditioned media after treating PDAC cells with hyaluromycin. We demonstrate that hyaluromycin inhibits proliferation and migration of PDAC cells. We also found that these antitumor effects of hyaluromycin were associated with a decreased concentration of LMW-HA and a decreased phosphorylation of ribosomal protein S6. Our results suggest that hyaluromycin is a promising new drug against this highly aggressive neoplasm.

Here, we report the draft genome sequence of an anthracimycin producer, Streptomyces sp. TP-A0875. The genome contains at least two type I polyketide synthase (PKS) gene clusters, two type II PKS gene clusters, and three nonribosomal peptide synthetase gene clusters. The gene cluster for anthracimycin biosynthesis was identified based on the PKS domain organization.

Natural products obtained from marine invertebrates such as sponges and tunicates are attractive sources of drugs. However, a critical obstacle in the development of these compounds is the problem of supply. In most cases, neither chemical synthesis nor mariculture of invertebrates is economically feasible. Due to structural similarities, many marine natural products are suspected to be produced by associated microorganisms. A favorable strategy for the production of such compounds is to use culturable microorganisms. Here we report that didemnin B, a tunicate-derived depsipeptide, has been isolated from a culturable bacterium, Tistrella mobilis YIT 12409.

Streptomyces sp. TP-A0867 (=NBRC 109436) produces structurally complex polyketides designated alchivemycins A and B. Here, we report the draft genome sequence of this strain together with features of the organism and assembly, annotation, and analysis of the genome sequence. The 9.9 Mb genome of Streptomyces sp. TP-A0867 encodes 8,385 putative ORFs, of which 7,232 were assigned with COG categories. We successfully identified a hybrid polyketide synthase (PKS)/ nonribosomal peptide synthetase (NRPS) gene cluster that could be responsible for alchivemycin biosynthesis, and propose the biosynthetic pathway. The alchivemycin biosynthetic gene cluster is also present in Streptomyces rapamycinicus NRRL 5491T, Streptomyces hygroscopicus subsp. hygroscopicus NBRC 16556, and Streptomyces ascomycinicus NBRC 13981T, which are taxonomically highly close to strain TP-A0867. This study shows a representative example that distribution of secondary metabolite genes is correlated with evolution within the genus Streptomyces.

Here, we report the draft genome sequence of Micromonospora sp. DSW705 (=NBRC 110037), a producer of antitumor cyclic depsipeptides rakicidins A and B, together with the features of this strain and generation, annotation, and analysis of the genome sequence. The 6.8 Mb genome of Micromonospora sp. DSW705 encodes 6,219 putative ORFs, of which 4,846 are assigned with COG categories. The genome harbors at least three type I polyketide synthase (PKS) gene clusters, one nonribosomal peptide synthetase (NRPS) gene clusters, and three hybrid PKS/NRPS gene clusters. A hybrid PKS/NRPS gene cluster encoded in scaffold 2 is responsible for rakicidin synthesis. DNA database search indicated that the biosynthetic gene clusters for depsipeptides bearing 4-amino-2,4-pentadienoate are widely present in taxonomically diverse actinomycetes.