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Synthetic biology breakthrough leads to cheaper statin production

Date:
February 27, 2015
Source:
Manchester University
Summary:
Researchers have developed a single-step fermentative method for the production of leading cholesterol-lowering drug, pravastatin, which will facilitate industrial-scale statin drug production.
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University of Manchester researchers, together with industrial partner DSM, have developed a single-step fermentative method for the production of leading cholesterol-lowering drug, pravastatin, which will facilitate industrial-scale statin drug production.

In a study published in Proceedings of the National Academy of Sciences, the researchers have devised a single-step fermentative method for the industrial production of the active drug pravastatin that previously involved a costly dual-step fermentation and biotransformation process.

Reprogramming the antibiotics-producing fungus Penicillium chrysogenum, with discovery and engineering of a cytochrome P450 enzyme involved in the hydroxylation of the precursor compactin, enabled high level fermentation of the correct form of pravastatin to facilitate efficient industrial-scale statin drug production.

Key steps leading to the successful outcome included the identification and deletion of a fungal gene responsible for degradation of compactin, in addition to evolution of the P450 to enable it to catalyse the desired stereoselective hydroxylation step required for high level pravastatin production.

Statins are successful, widely used drugs that decrease the risk of coronary heart disease and strokes by lowering cholesterol levels. The development of this group of drugs has been one of the major breakthroughs in human healthcare over the last two decades.

Statins have their origins in the discovery of a fungal natural product (compactin), which was shown to have good cholesterol lowering properties. Since compactin itself was not stable enough for clinical use, derivatives were created and other molecules with a similar mode of action were prepared to provide useful drugs.

Professor Andrew Munro based at the Manchester Institute of Biotechnology at The University of Manchester said: "This research marks a significant breakthrough and forms the basis of a patented process for the efficient production of this blockbuster drug. These results are the first example of harnessing the potential of a previously improved industrial production strain which can be used in the rapid development of other novel production strains for unrelated chemicals.

"The data also highlight how protein engineering can be exploited in synthetic biology applications towards industrial scale production of valuable pharmaceuticals."

The paper 'Single-step fermentative production of the cholesterol-lowering drug pravastatin via reprogramming of Penicillium chrysogenum', was published in Proceedings of the National Academy of Sciences.


Story Source:

Materials provided by Manchester University. Note: Content may be edited for style and length.


Journal Reference:

  1. Kirsty J. McLean, Marcus Hans, Ben Meijrink, Wibo B. van Scheppingen, Aad Vollebregt, Kang Lan Tee, Jan-Metske van der Laan, David Leys, Andrew W. Munro, Marco A. van den Berg. Single-step fermentative production of the cholesterol-lowering drug pravastatin via reprogramming ofPenicillium chrysogenum. Proceedings of the National Academy of Sciences, 2015; 201419028 DOI: 10.1073/pnas.1419028112

Cite This Page:

Manchester University. "Synthetic biology breakthrough leads to cheaper statin production." ScienceDaily. ScienceDaily, 27 February 2015. <www.sciencedaily.com/releases/2015/02/150227084313.htm>.
Manchester University. (2015, February 27). Synthetic biology breakthrough leads to cheaper statin production. ScienceDaily. Retrieved May 26, 2017 from www.sciencedaily.com/releases/2015/02/150227084313.htm
Manchester University. "Synthetic biology breakthrough leads to cheaper statin production." ScienceDaily. www.sciencedaily.com/releases/2015/02/150227084313.htm (accessed May 26, 2017).

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