PMID: 11927262Apr 3, 2002Paper

Hexaene derivatives of nystatin produced as a result of an induced rearrangement within the nysC polyketide synthase gene in S. noursei ATCC 11455

Chemistry & Biology
Trygve BrautasetSergey Zotchev

Abstract

Genetic manipulation of the polyketide synthase (PKS) gene nysC involved in the biosynthesis of the tetraene antifungal antibiotic nystatin yielded a recombinant strain producing hexaene nystatin derivatives. Analysis of one such compound, S48HX, by LC-MS/MS suggested that it comprises a 36-membered macrolactone ring completely decorated by the post-PKS modification enzymes. Further characterization by bioassay has shown that S48HX exhibits antifungal activity. Genetic analysis of the hexaene-producing mutant revealed an in-frame deletion within the nysC gene via recombination between two homologous ketoreductase domain-encoding sequences. Apparently, this event resulted in the elimination of one complete module from NysC PKS, subsequently leading to the production of the nystatin derivative with a contracted macrolactone ring. These results represent the first example of manipulation of a PKS gene for the biosynthesis of a polyene antibiotic.

References

Apr 1, 1997·Current Opinion in Biotechnology·H G Nam
Nov 11, 1999·Medicinal Research Reviews·L Katz, R McDaniel
Feb 20, 2002·Chemical Reviews·David A. Hopwood

❮ Previous
Next ❯

Citations

Feb 9, 2005·Applied Microbiology and Biotechnology·Espen Fjaervik, Sergey B Zotchev
Aug 13, 2005·Journal of Industrial Microbiology & Biotechnology·Mi-Yeon LeeEung-Soo Kim
Aug 22, 2009·Journal of Industrial Microbiology & Biotechnology·Byung-Gyun KimEung-Soo Kim
Dec 10, 2003·Current Opinion in Biotechnology·Benjamin N Mijts, Claudia Schmidt-Dannert
Dec 10, 2002·Current Opinion in Chemical Biology·Nicola L Pohl
Sep 26, 2013·Journal of Industrial Microbiology & Biotechnology·Janko DiminicJurica Zucko
Apr 17, 2003·Applied Microbiology and Biotechnology·J F AparicioS B Zotchev
Jan 13, 2010·European Journal of Mass Spectrometry·Ales UlrychVladimir Havlicek
Apr 3, 2007·Applied and Environmental Microbiology·Mimmi Throne-HolstSergey B Zotchev
Aug 2, 2003·Critical Reviews in Biotechnology·Christopher D Reeves
Jan 5, 2021·Applied Microbiology and Biotechnology·Simona Barbuto FerraiuoloOdile Francesca Restaino

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.