Inhibitory Effects of Diketopiperazines from Marine-Derived Streptomyces puniceus on the Isocitrate Lyase of Candida albicans.

The glyoxylate cycle is a sequence of anaplerotic reactions catalyzed by the key enzymes isocitrate lyase (ICL) and malate synthase, and plays an important role in the pathogenesis of microorganisms during infection. An icl-deletion mutant of Candida albicans exhibited reduced virulence in mice compared with the wild type. Five diketopiperazines, which are small and stable cyclic peptides, isolated from the marine-derived Streptomyces puniceus Act1085, were evaluated for their inhibitory effects on C. albicans ICL. The structures of these compounds were elucidated based on spectroscopic data and comparisons with previously reported data. Cyclo(L-Phe-L-Val) was identified as a potent ICL inhibitor, with a half maximal inhibitory concentration of 27 µg/mL. Based on the growth phenotype of the icl-deletion mutants and icl expression analyses, we demonstrated that cyclo(L-Phe-L-Val) inhibits the gene transcription of ICL in C. albicans under C2-carbon-utilizing conditions.

nonG, a constituent of the nonactin biosynthetic gene cluster, regulates nocardamine synthesis in Streptomyces albus J1074.

Many factors regulate the expression of specialised secondary metabolite biosynthetic gene clusters, which have been recognised as important for the discovery of novel microbial natural products. A cosmid library based on genomic DNA of the marine-derived Streptomyces puniceus Act1085 was constructed and screened to identify a short gene cluster similar to the nonactin biosynthetic cluster. The ORFs of the gene cluster isolated had high amino acid sequence identity, from 82% to 96%, with corresponding ORFs of the nonactin biosynthetic gene cluster from S. griseus subsp. griseus ETH A7796. Despite the expectation that nonactin or its derivatives would be made from heterologous expression of the gene cluster found in S. albus J1074, nocardamine was isolated. The heterologous expression data indicate that the production of nocardamine in S. albus J1074 is due to an ortholog of nonG, a TetR family transcriptional regulator, from S. puniceus Act1085.

Absolute Configurations of Griseorhodins A and C.

The known antibiotic and cytotoxic compounds griseorhodin A (1) and griseorhodin C (2) were produced in solid culture by Streptomyces puniceus AB10, which was isolated from the leaf-cutter ant Acromyrmex rugosus rugosus. Their absolute configurations were unambiguously established as 6S,6aR,7S,8S and 6R,6aR,7S,8R, respectively, using vibrational circular dichroism (VCD) and density functional theory (DFT) calculations.

Streptomyces puniceus strain AS13., Production, characterization and evaluation of bioactive metabolites: A new face of dinactin as an antitumor antibiotic.

A highly active actinobacterial strain isolated from untapped areas of Northwestern Himalayas and characterised as Streptomyces puniceus strain AS13 by 16S rRNA gene sequencing was selected for production of bioactive metabolites. The bioassay-guided fractionation of microbial cultured ethyl acetate extract of the strain, led to isolation of macrotetrolide compound 1 (Dinactin) and compound 2 (1-(2,4-dihydroxy-6-methylphenyl)-ethanone). Structures of the isolated compounds were elucidated by [corrected] interpretation of NMR and other spectroscopic data including HR-ESI-MS, FT-IR. These compounds are reported for first time from Streptomyces Puniceus. Compound 1 exhibited strong anti-microbial activity against all tested bacterial pathogens including Mycobacterium tuberculosis. The MIC values of compound 1 against Gram negative and Gram positive bacterial pathogens ranged between 0.019 - 0.156µgml-1 and 1µgml-1 against Mycobacterium tuberculosis H37Rv. Dinactin exhibited marked anti-tumor potential with IC50 of 1.1- 9.7µM in various human cancerous cell lines and showed least cytotoxicity (IC50∼80µM) in normal cells (HEK-293). Dinactin inhabited cellular proliferation in cancer cells, reduced their clonogenic survival as validated by clonogenic assay and also inhabited cell migration and invasion characteristics in colon cancer (HCT-116) cells. Our results expressed the antimicrobial potential of dinactin and also spotted its prospective as an antitumor antibiotic.