Fermentation Penicillium citrinum

Pravastatin (47) and Mevastatin (48) are anticholesterol drugs which act by competitively inhibiting HMG Co A reductase [75], Pravastatin sodium is produced by two fermentation steps. The first step is the production of compound ML-236B by Penicillium citrinum [75-77], The purified compound was con-... 

Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme in the cholesterol biosynthetic pathway (Fig. 1). In contrast to desmosterol and other late-stage lipid-soluble intermediates, HMG is water-soluble, and there are alternative metabolic pathways for its breakdown when HMG-CoA reductase is inhibited so that there is no buildup of potentially toxic precursors. Therefore, of the more than 30 enzymes involved in the biosynthesis of cholesterol, HMG-CoA reductase was a natural target. Substances that have a powerful inhibitory effect on this enzyme, including ML236B (compactin), were first discovered by Endo in a fermentation broth of Penicillium citrinum in the... 

Pravastatin (10) is another HMG-CoA reductase for the inhibition of cholesterol biosynthesis it is marketed by Sanyo and Bristol Myers Squibb under the trade names Mevalotin and Pravachol.87 It has a close structural relationship to lovastatin and simvastatin. It is produced by a two-step sequence. First, mevastatin (11), also known as ML-236B or compactin, is prepared by fermentation of Penicillium citrinum ss it is then enzymatically hydroxylated to produce 11 (Scheme 31.7).88-101... 

Quantitative distribution and optical purities of the secondary alcohols obtained after fermentation with Penicillium citrinum are very similar to those isolated from coconut or corn (Figure 4). A combination of stereospecific reduction and following enantioselec-tive metabolization may be one of the keys to explain the ratios of enantiomers of aliphatic secondary alcohols observed in natural systems. 

For the preparation of pravastatin (Mevalotin , Sankyo), at first mevastatin is obtained from fermentation of Penicillium citrinum its regio- and stereo-selective enzymatic hydroxylation can be achieved with a number of different microbial strains Mucor hiemalis, Penicillium coccineus, Rhizoctonia solani or Nocar-dia. Streptomyces carbophilus is used today to produce mevastatin under optimised conditions a productivity of around 5 g/1 or even higher can be obtained. [392]... 

Novel quinolone antibiotics, quinolactacins A-C (Schemes 24.22 and 24.23 Table 24.28) were first discovered from the cultured broth of Penicillium sp. EPF-6, which was isolated from the larvae of the mulberry pyralid (Margaronia pyloalis Welker) [41]. More recently, the two quinolactacin A diastereomers were isolated from solid-state fermentation of Penicillium citrinum 90648 and named... 

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