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International audience; Members of the Streptomyces genus are among the most prolific microorganisms producing secondary metabolites with wide uses in medicine and in agriculture. Sequencing of the genome of the model Streptomyces, Streptomyces coelicolor, has highlighted an unexpected feature, i.e. that the potential of these organisms to synthesise secondary metabolites has been largely underestimated. They indeed possess many more gene clusters encoding natural product-like biosynthetic pathways than there are known natural products. Similar observations have since been made for other bacterial or fungal genomes. Thus, it became clear that microbial secondary metabolism had been seriously underestimated and that genome-based approaches were very promising for the search of new bioactive compounds. Here, we present an overview of the secondary metabolite biosynthetic potential of Streptomyces ambofaciens, a species known for decades as producer of the macrolide spiramycin and the pyrrolamide congocidine. Interestingly, genome analysis has revealed that despite of the close phylogenetic relatedness between S. coelicolor and S. ambofaciens, most of its secondary metabolite gene clusters are species-specific.