Gateway enzyme could reduce pharma active production costs

Discovery opens up the prospect of producing the API and other chemicals more cheaply and efficiently

Scientists have discovered an enzyme used by nature to make powerful chemicals ranging from a cancer drug (vinblastine) to catnip. The discovery opens up the prospect of producing the API and other chemicals more cheaply and efficiently.

The anticancer ingredient vinblastine sulphate is currently derived from the Madagascar periwinkle plant. An enzyme known as iridoid synthase is an essential step in the production of this compound. But vinblastine can be produced only in very low yields and the drug has many side-effects. Scientist would like to produce it more efficiently and to lessen any side-effects.

The molecular backbone of all iridoids consists of two fused rings and scientists have been trying to track down what makes this ring system. Experiments showed that iridoid synthase is the enzyme responsible. Scientists believe that a better understanding of how the iridoid synthase works could open up new ways to make pharmaceutical compounds using synthetic biology.

The study, published in Nature in November 2012,1 was led by UK-based scientists from the John Innes Centre, an institute on Norwich Research Park. ‘We need to identify more enzymes to see the entire pathway used in nature to make this potent compound,’ says Dr O’Connor. ‘But the enzyme we have discovered is also the basic scaffold for many other iridoid chemicals and we can start to experiment with building new chemical structures with biological activity.’

O’Connor and her co-workers will now investigate whether the enzyme is important in the widely used Diels-Alder reaction.

Reference

1. An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis. Nature, DOI: http://dx.doi.org/10.1038/nature11692

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