Part of a natural compound that can lower cholesterol has been made by cloning a fungal gene, according to scientists from the University of Bristol and GlaxoSmithKline, UK.

Squalestatin is a fungal compound from the polyketide family. Polyketides occur naturally in bacteria, fungi and plants and are important drugs for both humans and animals. Unfortunately, their chemistry is very complex, making it uneconomical to synthesise them commercially. However, polyketides made by bacteria can be prepared on a large scale if bacterial genetics are used to increase the yields of useful compounds from fermentations; something that has not yet been possible for fungal polyketides like squalestatin due to a lack of appropriate genetic tools for fungi.

By understanding the mechanism for making fungal polyketides, Russell Cox?s team managed to clone a gene involved in squalestatin synthesis. ?Our strategy involved the transfer of the biosynthetic gene.to a different fungal host, where the gene was activated, resulting in the production of the polyketide synthase protein, which then made the tetraketide fragment of squalestatin,? explains Cox.

Caroline Evans