Sept. 24 (UPI) — In 1928, scientist Alexander Fleming discovered the first antibiotic, penicillin. The antibiotic was produced by a mold that had started growing in a Petri dish in Fleming’s lab.
Now, nearly a century later, scientists have successfully sequenced the genome of the original mold, a member of the genus Penicillium, and compared it those of later penicillin-producing molds.
The analysis, published Thursday in the journal Scientific Reports, showed the mold strains used to produce penicillin industrially in the United States and Europe synthesize the antibiotic in slightly different ways.
The discovery could help researchers develop new techniques for producing antibiotics at industrial scales.
“We originally set out to use Alexander Fleming’s fungus for some different experiments, but we realized, to our surprise, that no-one had sequenced the genome of this original Penicillium, despite its historical significance to the field,” lead researcher Timothy Barraclough, an evolutionary biologist and professor at both Oxford University and Imperial College London, said in a news release.
After Fleming’s discovery, drug makes began using mold from moldy cantaloupes to produce penicillin, selecting from strains with the greatest antibiotic production volumes.
To sequence the genome of Fleming’s Penicillium mold, researchers allowed a frozen sample from the original mold to regenerate before extracting DNA.
When comparing Fleming’s mold to modern strains, researchers focused on genes that regulate the enzymes responsible for penicillin production. Scientists also paid close attention to the genes that regulate the production of said enzymes.
Molds evolved penicillin production in response to the threat of invading microbes. Scientists suspect differences in the microbial threats in the United States and Europe caused the industrial mold strains — and the wild Penicillium molds from which they’re derived — to evolve slightly different antibiotic production enzymes.
Researchers hope followup studies will offer additional insights into how genetic differences between the two mold strains influence regulation of penicillin-producing enzymes.
“Our research could help inspire novel solutions to combating antibiotic resistance. Industrial production of penicillin concentrated on the amount produced, and the steps used to artificially improve production led to changes in numbers of genes,” said first study author Ayush Pathak, computational biologist at Imperial.
“But it is possible that industrial methods might have missed some solutions for optimizing penicillin design, and we can learn from natural responses to the evolution of antibiotic resistance,” Pathak said.