Combining the innovations of synthetic biology with biology and chemistry, a team of scientists at the University of Bristol have generated a brand-new platform that will allow the production of desperately needed brand-new antibiotics.
With resistance growing to existing antibiotics, there is a vital and urgent need for the discovery and development of new antibiotics that are cost effective.
Promising developments are derivatives of the antibiotic pleuromutilin, with the core pleuromutilin isolated from the mushroom Clitopilus passeckerianus.
Pleuromutilin derivatives are potent antibacterial drugs but often require difficult chemical modifications.
In a new paper published today in Nature Communications, the Bristol team report the genetic characterisation of the steps involved in pleuromutilin biosynthesis through heterologous expression and generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic activity.
This was achieved by taking the complete genetic pathway for pleuromutilin production, containing seven genes, from the mushroom, and rebuilding it in the industrially useful filamentous fungus Aspergillus oryzae, traditionally used to make soy sauce.
This then generated a unique platform of Aspergillus lines with combinations of the pathway genes to allow new compounds to be synthesized.
Professor Chris Willis, from the School of Chemistry, said: "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."
These new compounds are some of the only new class of antibiotics to join the market recently as human therapeutics.
Furthermore, with their novel mode of action and lack of cross-resistance, pleuromutilins and their derivatives represent a class with further great potential, particularly for treating resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and extensively drug resistant tuberculosis (XTB).
Professor Gary Foster from the School of Biological Sciences who led the team, with Dr Andy Bailey, added: "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.
"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."
Gary Foster | EurekAlert!
Record levels of mercury released by thawing permafrost in Canadian Arctic
13.12.2018 | University of Alberta
Stanford researcher deciphers flows that help bacteria feed and organize biofilms
13.12.2018 | Stanford University
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
13.12.2018 | Physics and Astronomy
13.12.2018 | Earth Sciences
13.12.2018 | Life Sciences