Pravastatin is one of the most popular cholesterol-lowering drugs. Its industrial production represents a two-stage process including the microbial production of compactin and its further biocatalytic conversion to pravastatin. To increase a conversion rate, a higher compactin content in fermentation medium should be used; however, high compactin concentrations inhibit microbial growth. Therefore, the improvement of the compactin resistance of a producer still remains a relevant problem. A multi-step random UV mutagenesis of a Streptomyces xanthochromogenes strain RIA 1098 and the further selection of high-yield compactin-resistant mutants have resulted in a highly productive compactin-resistant strain S 33-1. After the fermentation medium improvement, the maximum bioconversion rate of this strain has reached 91 % at the daily compactin dose equal to 1 g/L and still remained high (83 %) even at the doubled dose (2 g/L). A 1-year study of the mutant strain stability has proved a stable inheritance of its characteristics that provides this strain to be very promising for the pravastatin-producing industry.

/pdf/strain-improvement-of-streptomyces-xanthochromogenes-ria-1ckk2yq34w.pdf

Strain Improvement of Streptomyces xanthochromogenes RIA 1098 for Enhanced Pravastatin Production at High Compactin Concentrations.

Hypercholesterolemia is considered to be an important risk factor in coronary heart disease. Statins has received a lot of attention in recent years due to control of cholesterol biosynthesis and level of cholesterol in the body, by inhibiting the enzyme 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. Inhibition results in reduced levels of mevalonate in the body, leading to pleiotropic effects. Compactin and its hydroxy derivative pravastatin are natural statins and are used as hypocholesterolemic agents which are potent inhibitors of HMG-CoA reductase activity. Pravastatin was more effective drug than compactin. Various fungi and bacteria have been used for the commercial production of pravastatin. Using different strategies for improving production levels, yields have been increased more than the amount originally produced. Recently, the gene sequencing is responsible for pravastatin production has been cloned and sequenced. It has been incorporated into other fungal or bacterial species for better compactin resistant as well as for maximum bioconversion rate. This review deals with the structure and chemistry, applications, mode of action, bioconversion, and production of pravastatin. This review is an effort to compile the available information on various aspects of pravastatin.

Bioconversion of mevastatin to pravastatin by various microorganisms and its applications – A review

The present invention provides two new microorganism strains of Saccharothrix, designated as YS-44442 and YS-45494, a process of producing pravastatin using the strains, and an improved process for isolation of (HMG)-CoA reductase inhibitors.

Strains of saccharaothrix, process for producing pravastain using the strains and isolation process of (HMG)-CoA reductase

A method of isolating or purifying plavastatin or its pharmacologically acceptable salt characterized by involving, in the process of isolating or purifying plavastatin or its pharmacologically acceptable salt, the step of extracting plavastatin by using an organic solvent represented by the formula CH3CO2R (wherein R represents alkyl having 3 or more carbon atoms) or the step of decomposing impurities by using an inorganic acid/an inorganic base; and compositions containing plavastatin sodium thus obtained.

Method of purifying plavastatin

A process for the isolation or purification of pravastatin or a
pharmacologically acceptable salt thereof comprising decomposing impurities using
an inorganic base.

Process for the purification of pravastatin

The present invention relates to a new microbial process for the preparation of compound of formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged culture of a strain which is able to 6β-hydroxylate the compound of formula (II) in aerobic fermentation and by the separation and purification of the product of formula (I) formed in the course of the bioconversion. The latter comprises the cultivation of a Micromonospora strain which is able to 6β-hydroxylate a compound of general formula (II) - wherein R is as defined above - at 25-32 °C on a nutrient medium containing available carbon - and nitrogen sources and mineral salts, thereafter feeding the substrate to be transformed into the developing culture, then hydroxilating the substrate until finishing of the bioconversion, then separating the compound of formula (I) from the culture broth and, if desired, purifying the same.

Hydroxylation of compactin to pravastatin by micromonospora

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Hydroxylation of compactin to pravastatin by micromonospora