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.Sponges are multicellular invertebrates and sessile filter feeders which are abundant in the oceans as well as in freshwater habitats (41). They gained great interest due to their association with a wide variety of microorganisms. These microorganisms are known to be a rich source of secondary metabolites (108), which exhibit a broad range of bioactivities such as inhibition of enzyme activities and cell division and antiviral, antimicrobial, anti-inflammatory, antitumor, cytotoxic, and cardiovascular properties (77).Numerous studies concerning specific aspects of spongebacterium associations were accomplished using distinct methods for the evaluation of the microbial diversity (mostly molecular approaches) or the bioactivities (culture-dependent methods) or biosynthetic aspects (chemical analyses and molecular approaches) of secondary metabolites of the associated bacteria (19,47,51,54,110,122,126). So far, there is less comprehensive information about the integration of this knowledge into concepts for sponge-bacterium interactions based on small molecules.We focused on Actinobacteria associated with Halichondria panicea Pallas (Porifera, Demospongiae, Halichondriida, Halichondriidae), a sponge species living in coastal habitats worldwide (9). Previous work demonstrated a phylogenetically diverse array of bacterial groups present in this sponge: representatives of Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Cytophaga/Flavobacteria, the Deinococcus group, low-GϩC-content Gram-positive bacteria, Actinobacteria, and Planctomycetales were identified by means of a genetic ...