earticle

영어

Polyene macrolides are mostly produced by Streptomycetes and some other soil bacteria and exert their fungicidal action via interaction with membrane sterols, resulting in the formation of highly organized hydrophilic channels, through which small molecules and ions can leak out. Using the genomics-guided polyene screening method, a rare actinomycetes called Pseudonocardia autotrophica was previously identified to contain a functionally-clustered nystatin-like biosynthetic genes and to produce a presumably novel polyene compound named NPP. Many previous researches revealed that modification of the polyene structure through engineering of its biosynthetic genes is a promising strategy for the production of novel polyene derivatives suitable for potential pharmaceuticals. In our research, we have obtained new derivatives by engineering of genes related with both early and late stages of NPP biosynthetic pathways. This biosynthetic modification approach is already yielding sufficient amount of novel materials for testing the toxicity and bioactivity, thus opening possibilities for discovery of drug-leads for development of effective and safe pharmaceuticals.