Inga Kajahn

Comprehensive Investigation of Marine Actinobacteria Associated with the Sponge Halichondria panicea

ABSTRACT Representatives of Actinobacteria were isolated from the marine sponge Halichondria panicea collected from the Baltic Sea (Germany). For the first time, a comprehensive investigation was performed with regard to phylogenetic strain identification, secondary metabolite profiling, bioactivity determination, and genetic exploration of biosynthetic genes, especially concerning the relationships of the abundance of biosynthesis gene fragments to the number and diversity of produced secondary metabolites. All strains were phylogenetically identified by 16S rRNA gene sequence analyses and were found to belong to the genera Actinoalloteichus, Micrococcus, Micromonospora, Nocardiopsis, and Streptomyces. Secondary metabolite profiles of 46 actinobacterial strains were evaluated, 122 different substances were identified, and 88 so far unidentified compounds were detected. The extracts from most of the cultures showed biological activities. In addition, the presence of biosynthesis genes encoding polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) in 30 strains was established. It was shown that strains in which either PKS or NRPS genes were identified produced a significantly higher number of metabolites and exhibited a larger number of unidentified, possibly new metabolites than other strains. Therefore, the presence of PKS and NRPS genes is a good indicator for the selection of strains to isolate new natural products.

Scopularides A and B, Cyclodepsipeptides from a Marine Sponge-Derived Fungus, Scopulariopsis brevicaulis

Two novel cyclodepsipeptides, scopularides A and B, were found in the fungus Scopulariopsis brevicaulis, which was isolated from the marine sponge Tethya aurantium. In addition, the known fungal metabolite paxilline was identified. The structures of the scopularides were elucidated by NMR, MS, and chemical derivatization methods as cyclo-(3-hydroxy-4-methyldecanoyl-Gly-L-Val-D-Leu-L-Ala-L-Phe) and cyclo-(3-hydroxy-4-methyloctanoyl-Gly-L-Val-D-Leu-L-Ala-L-Phe) for scopularide A and B, respectively. Antibiotic activity against Gram-negative bacteria was absent and against Gram-positive bacteria was weak, but activity against several tumor cell lines was significant at 10 microg/mL.

Mayamycin, a Cytotoxic Polyketide from a Streptomyces Strain Isolated from the Marine Sponge Halichondria panicea

A new benz[a]anthracene derivative called mayamycin (1) was identified in cultures of Streptomyces sp. strain HB202, which was isolated from the marine sponge Halichondria panicea and selected because of its profound antibiotic activity. The ability to produce aromatic polyketides was indicated by genetic analyses, demonstrating the presence of a type II polyketide synthase. The production of mayamycin (1) was induced by variation of the culture conditions. The structure of 1 was elucidated by HPLC-UV/MS and NMR spectroscopy. Mayamycin (1) exhibited potent cytotoxic activity against eight human cancer cell lines and showed activity against several bacteria including antibiotic-resistant strains.