Development of a drug discovery approach from microbes with a special focus on isolation sources and taxonomy.

Abstract

After the successful discoveries of numerous antibiotics from microorganisms, frequent reisolation of known compounds becomes an obstacle in further development of new drugs from natural products. Exploration of biological sources that can provide novel scaffolds is thus an urgent matter in drug lead screening. As an alternative source to the conventionally used soil microorganisms, we selected endophytic actinomycetes, marine actinomycetes, and actinomycetes in tropical areas for investigation and found an array of new bioactive compounds. Furthermore, based on the analysis of the distribution pattern of biosynthetic gene clusters in bacteria together with available genomic data, we speculated that biosynthetic gene clusters for secondary metabolites are specific to each genus. Based on this assumption, we investigated actinomycetal and marine bacterial genera from which no compounds have been reported, which led to the discovery of a variety of skeletally novel bioactive compounds. These findings suggest that consideration of environmental factor and taxonomic position is critically effective in the selection of potential strains producing structurally unique compounds.