Finding new sources for bioactive compounds by genome mining of unique enzymology
A new "Angewandte Chemie" paper by the Piel and Fraaije (Groningen) groups introduces an approach to prioritize biosynthetic pathways rich in unique oxidation domains to identify culturable bacterial sources for natural products and enzymes from the complex class of trans-AT polyketide synthases.
Natural products derived from trans-AT polyketide synthases have an exceptional wide range of bioactivities. Many of them are produced by uncultured bacterial symbionts of marine invertebrates, which presents a supply problem for their further development as drug candidates. The functional diversity of the extremely complex enzymes that give rise to these bioactive compounds was mined in this work to specifically identify polyketides with oxidatively modified backbones. This approach led to the discovery of lobatamide from a microbial talented producer, the culturable plant symbiont Gynuella sunshinyii. Lobatamides are benzolactone enamides with a potent vacuolar (H+)-ATPase activity that interferes with tumor metastasis. Apart from its attractive bioactive product, the biosynthetic pathway for lobatamides has several enzymatic novelties that could potentially serve as a source for biocatalysis and for future engineering of intricate artificial polyketide synthases.
Link to the paper in external page Angewandte Chemie