Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria is associated with particular biosynthetic gene clusters (BGCs) in these microorganisms. The majority of these BGCs include
polyketide synthase (PKS) or
non-ribosomal peptide synthase (NRPS) or a combination of both PKS and NRPS.
Macrolides compounds contain a core macro-
lactone ring (aglycone) decorated with diverse functional groups in their chemical structures. The aglycon is generated by megaenzyme
polyketide synthases (PKSs) from diverse
acyl-CoA as precursor substrates. Further, post-PKS
enzymes are responsible for allocating the structural diversity and functional characteristics for their biological activities.
Macrolides are biologically important for their uses in
therapeutics as
antibiotics, anti-
tumor agents,
immunosuppressants, anti-parasites and many more. Thus, precise genetic/metabolic engineering of actinobacteria along with the application of various chemical/biological approaches have made it plausible for production of
macrolides in industrial scale or generation of their novel derivatives with more effective biological properties. In this review, we have discussed versatile approaches for generating a wide range of
macrolide structures by engineering the PKS and post-PKS cascades at either
enzyme or cellular level in actinobacteria species, either the native or heterologous producer strains.