Novel method for producing antibiotic introduced

Scientists from the University of Bristol have developed a new method for producing an antibiotic.

Pleuromutilin is an antibiotic that was discovered in the 1950s but until 2007 was not suitable for human use. It is currently prescribed for topical use only. Researchers managed to increase the output of pleuromutilin more than 2000% by expressing genes involved in the antibiotic’s production.

Gary Foster, Professor of molecular plant pathology at the University of Bristol said: “With this development, we are now ideally placed to develop novel derivatives and new antibiotics and produce them rapidly and cost effectively – something which is desperately needed globally.”

Derivatives of pleuromutilin are usually isolated from a mushroom called Clitopilus passeckerianus, a basidiomycete fungus. Pleuromutilin and its derivatives work by inhibiting protein synthesis through binding bacterial ribosomes. Due to their lack of cross-resistance they are ideally placed to treat methicillin-resistant Staphylococcus aureus and drug-resistant tuberculosis.

Researchers discovered a seven gene cluster was responsible for producing the antibiotic in C. passeckerianus. It was reconstructed within Aspergillus oryzae, a fungus belonging to a different fungus phylum, ascomycetes. This caused pleuromutilin production to increase by 2,106%.

This is the first gene cluster from a basidiomycete that has been successfully expressed in an ascomycete. Professor Foster said: “This was a massive team effort over many years to achieve this major breakthrough.  It involved, in the School of Biological Sciences, the drug discovery team led by myself and Dr Andy Bailey, with Dr Colin Lazarus on alternative expression platforms.

“In addition, significant effort came from chemists at the University of Bristol led by Professor Chris Willis and Professor Russell Cox, and collaborative scientists in GSK.“

The research was published in Scientific Reports.