Nanoparticle intervention of microbial metabolism for drug discovery

Natural products have been a rich source of inspiration for a diverse range of medical drugs with widely different chemical structures (e.g., terpenoids, alkaloids and phenolic compounds) and various biological activities. Microbes can produce a wide range of natural compounds, known as secondary metabolites. Increasingly, it has been recognized that microbes have an extensive range of gene clusters coding for secondary metabolites in which only some are transcribed, and the others remain silent and are not expressed in normal cultivation conditions. In the past years, great progress has been made in characterizing the gene clusters and understanding the biosynthetic pathways of secondary metabolites. Genetic engineering approaches have also been developed to manipulate secondary metabolism to enhance production of known secondary metabolites or discovery of new natural products. However, genetic engineering approach is time-consuming and often requires multiple cloning experiments and culture generations to achieve a suitable microbial strain. Recently, it has been demonstrated that NPs can be used as an elicitor to modulate microbial metabolic processes. Therefore, NPs intervention strategies for optimizing culture conditions affecting bacterial metabolism can be extremely useful for future drug discovery and development. Our preliminary research showed that the use of gold nanoparticles (AuNPs) under a specific cultivation method may activate silent biosynthetic pathways of a bacterial strain obtained from a potato common scab, where a novel gene cluster is activated or an existing gene cluster is enhanced to produce bioactive secondary metabolite. Subsequently, this bacterial strain was identified as Priestia megaterium (P. megaterium). Genome sequencing, bioinformatics approaches were applied to explore the potential secondary metabolites that might be produced by this bacterium. The culture of these bacteria was then intervened with different concentrations of AuNP to investigate if this intervention could promote the production of certain secondary metabolites, which were characterized and assessed for their anti-cancer effects on MDA-MB-231 breast cells using an MTT assay. Th genes that could potentially be associated with the production of these secondary metabolites were then assessed by RT-PCR to investigate the effects of AuNPs on gene expression associated with the metabolic pathways.