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Statin on a bioconveyor

26.04.2015

Statins are substances that inhibit a key enzyme that produces so-called bad cholesterol. Accordingly, its content in the blood falls, and with it the risk of atherosclerosis. A natural statin called compactin is found in mushrooms and was isolated by Endo Akiro in the mid-70s from a mold. However, it is inconvenient for pharmacists.

In the 80s, another statin, lovastatin, was discovered. It was also found in higher fungi, such as oyster mushrooms. In order not to force the population to eat huge amounts of mushrooms, chemists have come up with methods for synthesizing statins, and many doctors consider this the most important public health achievement in the last twenty years.

Synthesis, however, is complex and expensive, it involves several steps and subsequent purification. Biotechnology from the University of Manchester and DSM's Delft Biotechnology Center, led by Christie McLean and Marco van den Berg, managed to do it all in one step.

To do this, they reprogrammed an industrial strain of the mold Penicillium chrysogenum that produces antibiotics. First, the gene responsible for the decomposition of compactin was removed from it. Then they inserted the genes necessary for the efficient synthesis of compactin. Then they forced him to synthesize also cytochrome P450 of the bacterium Amycolatopsis orientalis, this protein turns compactin into one of the most effective statins - pravastatin. But this transformation went very badly, because the result was a mixture of stereoisomers, which are very expensive to separate.

The properties of cytochrome were altered by artificial selection, and eventually a process was achieved that synthesized the purest stereoisomer of pravastatin at six grams per liter of culture. This can already be implemented in production.

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