INV-20024
Microbes are a foundation of the discovery of bioactive molecules because they produce an enormous variety of secondary metabolites, some with desirable activities ranging from antibiotics to anti-inflammatory to anticancer to industrial enzymes. The advent of next-generation sequencing technologies uncovered that microbial genomes have genomic capacity far beyond that which had been discovered so far. However, most of the gene clusters that code for such metabolites are inaccessible because they are not expressed under artificial lab conditions.
For the past two decades, various approaches have been used to express the cryptic genes with few success stories and no approved drug. This invention suggests a simple method of controlled cultivation of microbes in their natural environment to induce “silent” genes to obtain novel and potentially valuable bioactive molecules for further discovery and utilization.
This invention is based on using a diffusion chamber to grow microorganisms in their natural habitat. Where the microbial strains with unknown cryptic genes are inoculated in the inner space and a semipermeable membrane separates strains from the environment but allows diffusion of chemicals from the environment such as growth factor.
This invention proposes to depart from the very idea of growing and exploring microbes in the lab, and move their cultivation to nature where the presence of natural friends and foes would induce the silent genes back into action. This simple idea has the potential to overcome the limitations of currently used approaches and provide a significant pipeline of novel, and previously undetectable, bioactive compounds.
If the cryptic gene clusters are being expressed by the free-living microbes, they will be expressed by microbes in the chamber offering an effortless way to express “silent” genes. The novel components encoded by the genes could be determined by bio-assay guided fractionation. Once grown in nature, the extracts can be screened against a panel of resistant tests species and any strain passing this assay is a producer of a novel antimicrobial coded by silent genes in the lab. This process can be further scaled up and utilized. The proposed method may lead to pipeline of novel chemical structures with desirable activities.
The benefits of this invention could be:
With further research this invention could be used for: