Penicillin Flavigenum

Study of penicillin fungi reveals great potential for new antibiotics

Tuesday 11 Apr 17
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by Anne Lykke

Want to know more about new antibiotics?

The project called IIMENA lead by Senior Scientist Tilmann Weber also dives into this field of new antibiotics with the focus on soil microbes and so-called co-cultivation.

 

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Even though the penicillin fungus provided the world with its first commercial antibiotic – penicillin – the fungus most likely still has a few tricks left up its sleeve, according to new research.

Antibiotic resistance is on everyone’s lips, and with an increasing number of disease-causing bacteria being able to survive today’s antibiotics, millions of patients are facing untreatable and potentially lethal infections.

But what if the penicillin fungus could once again save us from diseases, like back in the 1940’s when penicillin was first mass-produced?

New research – recently published in Nature Microbiology – shows that penicillin fungi harbor genes that encode hundreds of unknown so-called secondary metabolites, similar to penicillin.

The study was conducted by a team of researchers led by Jens Nielsen, Professor at Chalmers University of Technology in Gothenburg and Scientific Director at The Novo Nordisk Foundation Center for Biosustainability, DTU Biosustain, at Technical University of Denmark.

How to reveal the secret compounds of fungi

The tricky thing about secondary metabolites is that they are not vital to the fungus’ survival, but most often are expressed when the fungus tries to fight of enemies. Therefore, the compounds can be hard to detect in the lab.

Therefore, the research group analyzed the genomes of 24 different species of penicillin fungi to identify genes responsible for the production of secondary metabolites. 1300 pathways (i.e. clusters of genes that encode a secondary metabolite) were discovered, which averages to more than 50 pathways pr. species.

"It is actually very surprising that each fungus is able to express this many secondary metabolites, and it demonstrates the unexploited potential of these types of fungi when it comes to the discovery of new antibiotics"
Scientific Director Jens Nielsen, DTU Biosustain

This shows a big potential for fungi to produce a large variety of chemicals that could be used as antibiotics – and potentially other pharmaceuticals, explains Jens Nielsen:

“It is actually very surprising that each fungus is able to express this many secondary metabolites, and it demonstrates the unexploited potential of these types of fungi when it comes to the discovery of new antibiotics.”

Found a new version of a known antibiotic

In about 90 cases, the researchers were able to predict the chemical products of the pathways.

To demonstrate that the pathways actually led to a chemical, the researchers followed the production of the antibiotic yanuthone within different species expected to produce it. This analysis led to the identification of a new version of yanuthone made by two species not previously known to produce it.

All in all, the study shows a vast potential for fungi, not only in producing entirely new antibiotics but also in producing more efficient versions of older ones.

Next step for Jens Nielsen and his team is to insert the pathways of interest into yeast cells to study the compounds’ activity and ultimately be able to produce them in high quantities

Contact at Chalmers

PhD Student Jens Christian F. Nielsen, Department of Biology and Biological Engineering, Chalmers University of Technology. Mobile: +46(0)768-35 62 53, jens.c.nielsen@chalmers.se

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