medermycin and kalafungin

Medermycin and kalafungin, two antibacterial and antitumor antibiotics isolated from different streptomycetes, share an identical polyketide skeleton core. The present study reported the discovery of kalafungin in a medermycin-producing streptomycete strain for the first time. A mutant strain obtained through UV mutagenesis showed a 3-fold increase in the production of this antibiotic, compared to the wild type strain. Heterologous expression experiments suggested that its production was severely controlled by the gene cluster for medermycin biosynthesis. In all, these findings suggested that kalafungin and medermycin could be accumulated by the same streptomycete and share their biosynthetic pathway to some extent in this strain.

Topics: Anti-Bacterial Agents; Benzoquinones; Chromatography, High Pressure Liquid; Disk Diffusion Antimicrobial Tests; Magnetic Resonance Spectroscopy; Mass Spectrometry; Multigene Family; Mutagenesis; Naphthoquinones; Staphylococcus epidermidis; Streptomyces; Ultraviolet Rays

The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined. PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.

Topics: Alkylation; Antineoplastic Agents; Biomarkers; Cell Line, Tumor; Cell Proliferation; Cysteine; Humans; Lactones; Naphthoquinones; Oncogene Protein v-akt; Pyrans; Stereoisomerism; Structure-Activity Relationship

Topics: Animals; Anti-Bacterial Agents; Fermentation; Male; Naphthoquinones; Platelet Aggregation; Rats; Rats, Inbred Strains; Structure-Activity Relationship