Actinomycetes produces various secondary metabolite (SM). The discovery of novel SMs and expansion of utility of existing one by overproduction or targeted modification is effective approach. Nargenicin A1, an antibacterial polyketide produced by Nocardia sp.CS682, was enhanced by rational metabolic engineering and synthetic biological platform utilizing multi-monocistronic vector containing user defined parts and subsequent precursor refactoring strategy. After enhancement the antibacterial was subsequently glycosylated by efficient one vessel reaction systems containing glycosyltransferase (GT) from Bacillus licheniformis. Herboxidiene, a herbicidal cum antitumor compound produced by Streptomyces chromofuscus was structurally modified by hydroxylation/ epoxidation/glycosylation by using different substrate-flexible cytochrome P450s and glycosyltransferase. Pradimicin A is an angucyclic antifugal antibiotic produced by Actinomadura hibisca P157-2(ATCC53557). By insertional inactivation of two glycosyltransferase, pdmQ and pdmS, the exact order of glycosylation was determined alongwith generation of novel analogues. Thus, by utilizing different metabolic engineering and synthetic biological tools, the significant enhancement or diversification of their structure and functionality was attained in select Actinomycetes, which open up newer avenues for similar rational approaches in other strains for expanding the chemical diversity of natural products (NPs).
