Penicillin was one of the most important scientific discoveries of the 20th century, but its overuse is threatening to undo all that hard work. As more strains of bacteria become resistant to antibiotics, we need to develop new ones to stay ahead of the curve, but the fungi species that produce them can be hard to work with. Now scientists have used plain old baker's yeast to create penicillin molecules, and while that doesn't yet solve the resistance problem, it's a big step towards creating easy-to-tweak "mini-factories" for new forms of antibiotics and anti-inflammatory drugs.
Most antibiotics are made from nonribosomal peptides, which certain bacteria and fungi naturally produce. As we start running into trouble with the more common antibiotics, there's a need to experiment with new ones, but it's a slow process. Scientists are still figuring out which species are most promising, and learning how best to grow them in the lab.
And that's where yeast comes in. Being one of the first organisms to have its genome fully sequenced, scientists are very familiar with the genetic makeup of this fungus, meaning it's easy to grow and experiment with. Yeast could become an important platform for testing new antibiotics, and getting it to produce penicillin is a promising start.
"Humans have been experimenting with yeast for thousands of years," says Tom Ellis, co-author of the study. "From brewing beer to getting our bread to rise, and more recently for making compounds like anti-malarial drugs, yeast is the microscopic workhorse behind many processes."
For the new study, the team inserted fungi genes that normally produce penicillin into yeast cells. Sure enough, through a two-step biochemical reaction the yeast created its own penicillin, conveniently expelling it into the solution around it, saving the scientists the trouble of extracting it from the yeast cells. To test its effectiveness, they then put the solution in a Petri dish of streptococcus bacteria, and found that it was an active antibiotic.
"The rise of drug-resistant superbugs has brought a real urgency to our search for new antibiotics," says Ellis. "Our experiments show that yeast can be engineered to produce a well-known antibiotic. This opens up the possibility of using yeast to explore the largely untapped treasure trove of compounds in the nonribosomal peptide family to develop a new generation of antibiotics and anti-inflammatories."
It's a good start, but the researchers say there's still plenty of work to do. So far, the yeast doesn't make much of the drug, so the team wants to find ways to boost its productivity to more useful quantities. And of course, to tackle the superbug problem, they'll need to investigate whether yeast can be used to make more exotic antibiotics.
"Fungi have had millions of years to evolve the capability to produce bacteria-killing penicillin," says Ali Awan, co-author of the study. "We scientists have only been working with yeast in this context for a handful of years, but now that we've developed the blueprint for coaxing yeast to make penicillin, we are confident we can further refine this method to create novel drugs. We believe yeast could be the new mini-factories of the future, helping us to experiment with new compounds in the nonribosomal peptide family to develop drugs that counter antimicrobial resistance."
The research was published in the journal Nature Communications.
Source: Imperial College London