Pleuromutilins Fermentation, Structure and Biosynthesis

Englerin A, a Selective Inhibitor of Renal Cancer Cell Growth, from Phyllanthus engleri

“…It is well known that glycolic acid (GA), an important metabolite of ethylene glycol, causes acute renal toxicity in mammals 9. Hydroxy acid containing natural products are relatively rare; some of the known GA containing metabolites include pleuromutilin,10 saframycin R11 and an ecdysteroid from a Caribbean sponge 12. The NCI60 cell data13 for pleuromutilin indicated no significant cytotoxicity for this compound while saframycin R, although quite potent, did not show renal selectivity in the NCI60 cell panel 13.…”

Design and synthesis of molecular scaffolds with anti-infective activity

“…The pleuromutilin scaffold is readily available from biosynthetic fermentation 71 and has traditionally served as a practical starting point for many successful semi-synthesis efforts, complementing the fully synthetic approaches explored contemporaneously by several groups. 72 We recognized the extreme difficulty semi-synthetic approaches faced to chemically modify certain portions of the pleuromutilin skeleton, particularly the metabolically labile C-8 methylene and, taking inspiration from the binding mode observed by X-ray analysis, 70 we were inspired by the potential activity of simplified scaffolds like 131 (Figure 10) compared to the more heavily-substituted natural pleuromutilin 31 .…”

Effect of soybean oil on the production of mycelial biomass and pleuromutilin in the shake-flask culture of Pleurotus mutilis

“…Recently, a series of novel water-soluble pleuromutilin derivatives bearing a purine ring have been developed by Dainippon Sumitomo Pharma Co., Ltd (Hirokawa et al 2008a(Hirokawa et al , b, 2009a. Many researchers have investigated various methods to improve the production of pleuromutilin, for example, strain improvement by chemical mutagenesis (Papa et al 2006;Stewart 1986), nitrogen metabolism control (Knauseder and Brandl 1976), batch kinetics and modeling (Benkortbi et al 2007). However, the improvement of pleuromutilin production with carbon metabolism regulation has not been reported.…”