Studies on the Later Stage of the Biosynthesis of Pleuromutilin

Abstract

Mutilin (4) and deoxy analogues 2 and 3 are biosynthetic precursors of pleuromutilin (1) in the later stage of biosynthesis. Precursors 2 and 3 are required for studies on the oxygenation steps in biosynthesis, and were synthesized from readily available 1 via 4 by deoxygenation of the hydroxy groups. Feeding experiments with the 2 H-labeled precursors confirmed their microbial conversion into 1.

Biosynthetic Machinery of Diterpene Pleuromutilin Isolated from Basidiomycete Fungi

“…[ α ] =+13.2 ( c =1; CHCl 3 ). The optical rotation was in good agreement with the reported data …”

“…GC‐MS analysis of the metabolites of AO‐ ple34 showed the production of a new metabolite with m / z 290, the retention time and mass spectrum of which were identical to those of authentic premutilin (yield of product isolated: 37 mg L −1 in MPY medium; Figures S4 and S5). After purification, the structure was confirmed by 1 H NMR spectroscopic analysis in comparison with premutilin . These experiments proved that ple3 encoded a premutilin synthase.…”

“…In 2007, we synthesized 2 H‐labeled intermediates from 1 and conducted feeding experiments with the 1 ‐producing strain Clitopilus pseudo‐pinsitus . Effective incorporation of the deuterium atoms into 1 further confirmed the intermediacy of these compounds . Recently, the biosynthetic gene cluster of 1 was identified in Clitopilus passeckerianus , and reconstitution of the biosynthetic machinery in Aspergillus oryzae revealed the involvement of seven genes in the biosynthesis .…”

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

“…Symbols are for the mycelial biomass (m), pH (j) and pleuromutilin (u) into the cells and metabolized to the biosynthetical units of PHAs in A. eutrophus (Fukui and Doi 1998). Pleuromutilin belongs to the family of diterpenoid, its biosynthesis pathway followed the biogenetic isoprene rule and the C10 or C20 isoprenoid was the immediate precursors (McGarvey and Croteau 1995;Tsukagoshi et al 2007). Therefore, the accumulative long fatty acids might be used as the biosynthetical precursors for pleuromutilin formation through the channeling pathway.…”

Research and Development of New Drugs Against Tuberculosis

“…Pleuromutilins: Pleuromutilins represent a new kind of antibiotics derived from pleuromutiline, a bioactive diterpene initially isolated from edible Clitopilusscyphoidesfungus [44]. These molecules interfere with protein synthesis associating to the 23S rRNA unit.…”