Actinomycetes are known to produce over two-thirds of all known secondary metabolites. We review here recent progress in the metabolic engineering of streptomycetes for natural product biosynthesis. Several examples of the yield improvement of polyketides (mithramycin and tylactone) and non-ribosomal peptides (balhimycin and daptomycin) demonstrate the power of precursor supply engineering. Another example is the manipulation of a regulatory network for increased production of nystatin and teicoplanin. The second part highlights new approaches in the derivatization of natural products via combination of mutasynthesis and genomic engineering.
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