Scientific sequence of the genome of Alexander Fleming’s original penicillin-forming fungus. A team of researchers from Imperial College London, Oxford University, and CABI have successfully sequenced the genome of Alexander Fleming’s original fungal strain behind the discovery of penicillin.
Now classified as Penicillium rubens, and compared to two “highly productive” industrial strains of Penicillium rubens and the closely related species Penicillium nalgovens. While working at St Mary’s Hospital School of Medicine, Alexander Fleming discovered the first antibiotic, penicillin, which is now part of Imperial College London.
The antibiotic was manufactured by Penicillium rubens, later called Penicillium notetum, and more recently as Penicillium chrysogenum, when it accidentally started growing in a Petri dish. We were initially prepared to use Alexander Fleming’s mushrooms for a few different experiments.
But we realized, to our surprise, that no one had identified the genome of this original Penicillium, despite the historical importance of the region. Professor Timothy Barraclough of the Department of Life Sciences at Imperial College London and the Department of Zoology at the University of Oxford.
Although Alexander Fleming’s mold is known as the original source of penicillin, industrial production quickly shifted from cantaloupe melons in the United States to the use of fungi. From these natural beginnings, the penicillium samples were artificially selected for strains that produce large amounts of penicillin.
Penicillium rubens is recovered from the frozen specimen of Alexander Fleming. Professor Barraclough and his colleagues took Fleming’s original Penicillium rube from a frozen sample stored in a CABI culture collection and extracted DNA for sequencing.
The resulting genome was compared with the first published genome of two industrial Penicillium rubens strains used later in the United States. The researchers specifically looked at two types of genes: that encode the enzymes fungi use to make penicillin.
And those that regulate enzymes, for example, how many enzymes are made. The regulatory gene was the same genetic code in all strains, but the American strains had more copies of the regulatory gene, which helped those strains produce more penicillin.
However, the genes encoding penicillin-producing enzymes differ between strains isolated in the United Kingdom and the United States. Alexander Fleming sample in a tube. “This suggests that wild penicillium has evolved naturally in the United Kingdom and the United States to produce somewhat different versions of these enzymes,” the scientists said.
Molds like penicillium produce antibiotics to fight germs and are constantly in arms races as germs develop ways to bypass these defenses. British and American strains evolved separately to adapt to their local microbes.
Researcher in the Department of Life Sciences at Imperial College London, Dr Ayush Pathak said: Our research can help inspire novel solutions to combat antibiotic resistance. Industrial production of penicillin is focused on the quantity produced, and the steps used to artificially improve production led to a change in the number of genes.
But industrial methods may have overlooked some solutions to optimize penicillin design, and we can learn from natural reactions to the development of antibiotic resistance. The team’s results appear in the Journal of Scientific Reports.
Sir Alexander Fleming’s genome of penicillin-producing fungi revealed. The genome of Sir Alexander Fleming’s original penicillin-producing fungus has been observed for the first time. British scientists say this may lead to the development of new drugs to overcome resistance problems.
Penicillium chrysogenum is used in the production of antibiotics such as amoxicillin, ampicillin, cephalexin, and cefadrosil. First author Ayush Pathak, a master’s student at Imperial College London, said: ush our research can help inspire novel solutions to combat antibiotic resistance.
Its use to kill bacteria was discovered in 1928, when mold spores accidentally contaminated a Petri dish in the laboratory. Tests showed that it was safe for humans. An estimated 1 billion people worldwide take penicillin each year. Its overuse has led to the rise of deadly superbugs like MRSA.
The World Health Organization has rated antibiotic resistance as one of the greatest threats to humanity. Lead researcher Professor Timothy Barraclough, who works in the Imperial and Oxford Department of Zoology, said:
Basically, we are ready to use Alexander Fleming’s mushrooms for a few different experiments. But we find, to our surprise, that no one had sequenced the genome of this original Penicillium, even though it is historically important.
The team recultured Fleming’s frozen sample over fifty years old and then extracted the DNA for sequencing. It is housed in the Culture Collection at the Bioscience International Agriculture Center in Wallingford, Oxfordshire.
The resulting genome was compared to two industrial penicillium strains used later in the US derived from mushroom melons. They were found to use slightly different methods for penicillin production, possibly suggesting new routes for mass production.
The study published in Scientific Reports specifically looked at the genes that encode the enzymes that produce penicillin and those that regulate them. In both the United Kingdom and the United States, the genetic code of the regulatory genes was similar.
But there were more copies of American strains, which increased production. But the genes that code for penicillin-producing enzymes differ between strains isolated in the UK and the US. The researchers say it mirrors the wild penicillium in the UK and US that has evolved to produce slightly different versions of these enzymes naturally.
Molds like penicillium produce antibiotics to fight germs and are constantly in arms races as germs develop ways to bypass these defenses. Highlighting the genome opens the door to genetic manipulation. The UK and US strains probably evolved differently to suit their local microbes.
Microbial growth is a major problem today as many are becoming resistant to our antibiotics. Researchers do not yet know the results of different enzyme sequences in the UK and the US. But they say this increases the intriguing possibility of new ways to modify penicillin production.
Mr. Pathak said: Industrial production of hak penicillin focuses on the amount produced and has changed the number of genes that have been artificially used to improve production. But industrial methods may have overlooked some solutions to optimize penicillin design.
We can learn from natural reactions to the development of antibiotic resistance. While working at St. Mary’s Hospital School of Medicine, Fleming discovered the world’s first antibiotic, now part of Imperial.