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Advances in DNA sequencing technologies have made it possible to sequence large numbers of microbial genomes rapidly and inexpensively. In recent years, genome sequencing initiatives have demonstrated that actinomycetes with large genomes generally have the genetic potential to produce many secondary metabolites, most of which remain cryptic. Since the numbers of new and novel pathways vary considerably among actinomycetes, and the correct assembly of secondary metabolite pathways containing type I polyketide synthase or nonribosomal peptide synthetase (NRPS) genes is costly and time consuming, it would be advantageous to have simple genetic predictors for the number and potential novelty of secondary metabolite pathways in targeted microorganisms. For secondary metabolite pathways that utilize NRPS mechanisms, the small chaperone-like proteins related to MbtH encoded by Mycobacterium tuberculosis offer unique probes or beacons to identify gifted microbes encoding large numbers of diverse NRPS pathways because of their unique function(s) and small size. The small size of the mbtH-homolog genes makes surveying large numbers of genomes straight-forward with less than ten-fold sequencing coverage. Multiple MbtH orthologs and paralogs have been coupled to generate a 24-mer multiprobe to assign numerical codes to individual MbtH homologs by BLASTp analysis. This multiprobe can be used to identify gifted microbes encoding new and novel secondary metabolites for further focused exploration by extensive DNA sequencing, pathway assembly and annotation, and expression studies in homologous or heterologous hosts. [ABSTRACT FROM AUTHOR]

Natural products discovery from actinomycetes has been on the decline in recent years, and has suffered from a lack of innovative ways to discover new secondary metabolites within a background of the thousands of known compounds. Recent advances in whole genome sequencing have revealed that actinomycetes with large genomes encode multiple secondary metabolite pathways, most of which remain cryptic. One approach to address the expression of cryptic pathways is to first identify novel pathways by bioinformatics, then clone and express them in well-characterized hosts with known secondary metabolomes. This process should eliminate the tedious dereplication process that has hampered natural products discovery. Several laboratory and industrial production strains have been used for heterologous production of secondary metabolite pathways. This review discusses the results of these studies, and the pros and cons of using various Streptomyces and one Saccharopolyspora strain for heterologous expression. This information should provide an experimental basis to help researchers choose hosts for current application and future development to express heterologous secondary metabolite pathways in yields sufficient for rapid scale-up, biological testing, and commercial production. [ABSTRACT FROM AUTHOR]