Metabolic engineering of natural product biosynthesis in actinobacteria

•Advanced genomic manipulation tools in actinomycetes enable streamlined engineering of primary and secondary metabolism.•Advances in engineering of actinomycetes for production of complex natural products are reviewed.•Metabolic engineering of precursor supplies and regulatory network manipulation are important for achieving industrially relevant product titers.•Metabolic engineering of gene clusters is an innovative way of natural product derivatization.