Genome sequencing has accelerated our understanding about organization of biosynthetic clusters in bacterial genomes which are responsible for the production of secondary metabolites. These metabolites are sources of important drugs and act like anticancer, antibacterial and anti-infective agents. In this context actinomycetes are notable as nearly 70% of the economically important metabolites are produced by them. Genome sequences of many actinomycetes have suggested the presence of many cryptic biosynthetic gene clusters that are not expressed or poorly expressed [1]. These cryptic gene clusters may encode for novel products that can prove to be beneficial for mankind. In a recent study published in PNAS [2] Laureti et al. have identified one such cryptic gene cluster in genome of Streptomyces ambofaciens (producer of antibiotics-spiramycine and congocidine). This cluster is not associated with any metabolite production and is found to be poorly expressed. These workers expressed this cryptic gene cluster using large ATP-binding regulator of the LuxR family (LAL) protein, the members of which are known to be activator of pikromycin [3] and rapamycin [4]. NMR analysis of the expressed product suggested that the product is a novel macrolide which was named stambomycin. These workers identified four such macrolides-stambomycin A to D. Bioactivity of the novel macrolide suggested that the product can provide new insights into anticancer therapy owing to its antiproliferative activities against adenocarcinoma, human breast, lung and prostate cancer cell lines. Researchers have been looking for better drugs for treatment of antibiotic resistant strains and different types of cancers. This study has opened up new realms in the discovery of several novel natural products that find application in medicine.
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Lal, D., Lal, R. Discovering Metabolic Products of Cryptic Biosynthetic Pathways. Indian J Microbiol 51, 414 (2011). https://doi.org/10.1007/s12088-011-0188-0
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DOI: https://doi.org/10.1007/s12088-011-0188-0