A research team from the University of Bristol has combined the innovation of synthetic biology with chemistry to create a brand-new platform that will lead to the production of new antibiotics that are the derivatives of pleuromutilin, with the core pleuromutilin isolated from the mushroom Clitopilus passeckerianus.
Pleuromutilin derivatives are potent antibacterial drugs, but require difficult chemical modifications.
The researchers were able to take the complete genetic pathway for Pleuromutilin production—containing seven genes—from the mushroom and rebuild it in the industrially useful filamentous fungus Aspergillus oryzae.
This generated a new platform of Aspergillus lines with combinations of the pathway genes to allow scientists to synthesize new compounds.
“This is a classic case where nature has produced something really useful, but combining nature with chemistry through a synthetic biology approach we are able to make things even better,” Chris Willis, from the School of Chemistry, said in a statement.
There is a growing push for new antibiotics, as drug-resistant bacteria is becoming an increasingly dangerous problem.
Pleuromutilins and their derivatives have great potential for treating resistant strains including methicillin-resistant Staphylococcus aureus (MRSA) and extensively drug resistant tuberculosis (XTB) due to their novel mode of action and lack of cross-resistance.
“This research is very exciting as it also paves the way for future characterization of biosynthetic pathways of other basidiomycete natural products in ascomycete heterologous hosts,” Gary Foster, from the School of Biological Sciences, said in a statement. “Many mushrooms have never even been examined and act as an untapped resource.
“The platform also opens up new possibilities of further chemical modification for the growing class of potent antibiotics,” he added.