Efforts to optimize secondary metabolite production by manipulating nutritional or environmental factors in many cases enhanced secondary

metabolite biosynthesis leading to the Protease Inhibitor Library discovery of new natural products. In this context, production of novel natural products was achieved by applying the “OSMAC” (One Strain MAny Compounds) approach, which is based on the modification of easily accessible cultivation parameters including media composition, aeration, temperature or shape of culturing flask (Grond et al. 2002; Bode et al. 2002). Similarly, endophytic Paraphaeosphaeria quadriseptata was triggered to produce six new metabolites by using distilled instead of tap water for preparing the medium (Paranagama et al. 2007). Application of stress conditions may also influence secondary metabolite biosynthesis in microorganisms. UV mutagenesis as well as addition of tricyclazole, an inhibitor of dihydroxynaphthalene biosynthesis, to spirobisnaphthalene-producing Sphaeropsidales sp. resulted in the discovery of the 14-membered macrolide mutolide, thus indicating a possible impact of enzyme inhibitors on natural product

profiles (Bode et al. 2002). It is assumed that interaction between organisms inhabiting the same or different species underlies the observed vast diversity of natural products. Thus, the same approach may be applied to the laboratory by performing mixed Selleck NVP-BGJ398 fermentation experiments (Scherlach and Hertweck 2009). Challenging marine-derived Emericella sp. with the marine actinomycete Salinispora arenicola, in co-culture, induced production of two new cyclic depsipeptides, emericellamides A and B (Oh et al. 2007). Similarly, the soil-dwelling bacterium Streptomyces rapamycinicusthese was found to specifically activate a previously unrecognized PKS cluster in Aspergillus nidulans, which encoded for the production of orsellinic acid, its derivative

lecanoric acid, and the cathepsin K inhibitors Vildagliptin F-9775A and F-9775B, by modification of fungal histones (Nützmann et al. 2011). Chemical screening of extract libraries combined with genome sequencing studies represent a new powerful tool to predict chemical structures encoded by orphan genetic loci and hence may direct the search for new, relevant metabolites (Nguyen et al. 2008). While scanning Aspergillus nidulans genome sequence for putative biosynthesis genes three copies of genes encoding for proteins related to anthranilate synthase were detected. These enzymes catalyse the transformation of chorismate to anthranilic acid in tryptophane biosynthesis. Presence of multiple copies, however, indicated involvement in secondary metabolic pathways. As anthranilic acid is known as a precursor of quinazoline, quinoline and acridine alkaloids, A.