Research Areas
Biosynthesis and engineering of microbial secondary metabolites:
Our research activities include studies on antibiotic biosynthetic pathways and metabolic engineering in actinomycetes. The major original compounds under studies include anti-fungal aminocyclitol validamycin, insecticidal polyether ionophore nanchangmycin, anti-fungal heptaene macrolide candicidin, anti-parasitic macrolide meilingmycin, anti-tumor PKS-NRPS hybrid oxzolomycin, anti-fungal nucleoside peptide polyoxins and mildiomycin etc., all of which are of medicinal, agricultural and veterinary importance. Firstly, strategies for screening for potential clusters have been developed. Secondly, strategies are optimized for engineered over-production of important antibiotics and their most active components, which comprise heterologous expression of antibiotic gene clusters, expression of genes from other primary/secondary metabolic pathways with optimized codon usage, elimination of substrate competiting PKS gene clusters, and accumulation of most active components through domain silencing, etc. Thirdly, design of novel antibiotic derivatives is achieved through mutational biosynthesis, targeted domain/module inactivation or re-activation, combinatorial biosynthesis, and engineered pathway extension.