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PRAVASTATIN is a known 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA ) reductase inhibitor, widely used for the treatment of arteriosclerosis. Pravastatin is conventionally synthesized by a two-step fermentation procedure. Firstly Compactin is produced by Penicillium citrinum followed by the hydroxylation by Streptomyces carbophilus into Pravastatin.

Pravastatin, unlike other HMG-CoA reductase inhibitors such as Lovastatin and Simvastatin, which are administered as inactive pro-drugs requiring in vivo conversion to their active open hydroxy acid forms, has been developed for administration as the sodium salt of the active compound.

Initial conversion level in Streptomyces carbophilus strain when in 1996 year we started working at it was about 30%, t.i. only 30% of Compactin was reverted into Pravastatin. Our expertise in random mutagenesis by ultraviolet irradiation and chemical mutagens, screening and rational selection gave us opportunity to obtain fourteen months later first mutants with conversion rate of 45%. Up to now we have obtained mutants transforming about 55-65% of Compactin into Pravastatin in 3L fermentor. At the same time, we increased initial concentration of Compactin to be added. Productivity of the latest strains is about 12 G/L of Pravastatin.

Product:
Pravastatin

Potency:
Around 12 G/L

Scale:
Shake flasks, 3L fermentor, 30L fermentor

Fermentation time
120 - 144 hours (depends on strains)

Analysis method:
HPLC

Pravastatin Recovery Technology

Parameters for Recovery technology are as follows:

Yield: not less than 60%
Purity: not less then 98.5%

The novel process under development is a one-step fermentation using Penicillium citrinum transected with hydroxylase gene from Streptomyces carbophilus.

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