Hexaene Derivatives of Nystatin Produced as a Result of an Induced Rearrangement within the nysC Polyketide Synthase Gene in S. noursei ATCC 11455 (original) (raw)

N-7491 Trondheim embedded in the PKSs. Further modification of the polyene macrolactone ring via the action of monooxygen-2 SINTEF Applied Chemistry SINTEF ases and glycosyltransferases leads to the formation of a fully biologically active molecule [4]. Recently, a first N-7034 Trondheim 3 Institute for Cancer Research report on the engineered biosynthesis of a novel derivative of the polyene antibiotic pimaricin has been pub-and Molecular Biology Norwegian University of Science and Technology lished [5]. The data presented in this work confirm the importance of post-PKS modifications for the biological N-7489 Trondheim Norway activity of polyenes and provide further insight into the structure-function relationship of the polyene antibiotics. The properties of PKSs involved in the biosynthesis Summary of macrolide antibiotics make it possible to change their structure and embedded enzymatic activities in such Genetic manipulation of the polyketide synthase (PKS) a way that new compounds with predictable chemical gene nysC involved in the biosynthesis of the tetraene structures can be produced [6]. From this point of view, antifungal antibiotic nystatin yielded a recombinant the PKSs involved in the biosynthesis of polyene macrostrain producing hexaene nystatin derivatives. Analylide antibiotics are excellent targets for manipulation sis of one such compound, S48HX, by LC-MS/MS sugthat may provide novel antifungal agents with improved gested that it comprises a 36-membered macrolacpharmacological properties. tone ring completely decorated by the post-PKS