Review of genetics-free high-throughput approach for activating production of cryptic microbial secondary metabolites

Wenfa Ng
2019 Figshare  
Natural products account for a significant fraction of approved antibiotics, anti-inflammatory and anti-cancer drugs. Produced by complex biosynthetic pathways encoded by biosynthetic gene clusters (BGC), natural products remain a difficult class of compounds for study. Specifically, genome sequencing efforts have revealed many putative BGC with unknown secondary metabolites. Laboratory culture experiments, however, have failed to induce the expression of many BGC, where the expression level
more » ... expression level was either zero or very low levels under standard laboratory growth conditions. Different methods have been utilized in eliciting the expression of such silent BGC; however, most of the approaches either rely too heavily on time consuming genetic manipulations or require significant efforts in systematic study of culture conditions. Given the diversity of natural products and their chemical complexity that present particular challenges to instrumental analysis, difficulty also exists in profiling secondary metabolites. Thus, there is a need to develop high throughput facile methods for inducing the expression of silent BGC and visualizing the secondary metabolome generated. Writing in Nature Chemical Biology, Xu and coworkers described a genetics-free approach for high throughput activation and visualization of the cryptic metabolome of different natural products producing bacteria. Specifically, high throughput elicitors screening was coupled to imaging mass spectrometry where the latter help visualize the set of secondary metabolites activated by different inducers. By profiling for secondary metabolites from three bacterial species: Pseudomonas protegens Pf-5, Streptomyces, and actinomycetes, the work demonstrated the utility of the approach for different bacterial species and useful natural products were isolated from individual strains. For example, a novel lasso peptide was isolated from Streptomyces, while an antimicrobial and antiviral compound was obtained from actinomycetes. However, the [...]
doi:10.6084/m9.figshare.11437677.v1 fatcat:ldtpkox2z5eadf25z6srj6nk4q