Sequenced for the first time by the genome of an original mold producing penicillin

Alexander Fleming discovered the first antibiotic, penicillin, in 1928 while working at St Mary’s Hospital School of Medicine, now part of Imperial College London. The antibiotic was produced by a mold from the genus Penicillium that accidentally started growing in a petri dish. Now researchers at Imperial College London, CABI and the University of Oxford have sequenced the genome of Fleming’s original Penicillium strain using samples that were frozen alive more than fifty years ago. The team also used the new genome to compare Fleming’s mold with two Penicillium strains from the United States, which are used to produce the antibiotic on an industrial scale. The results, published today in Scientific Reports, show that both countries use different methods to produce penicillin.

Initially, we intended to use the Alexander Fleming mushroom for various experiments, but to our surprise, we realized that no one had sequenced the genome of this original Penicillium, despite its historical significance in the field.

Timothy Barraclough, study lead author

The team re-grown Fleming’s original Penicillium from a frozen sample stored in the culture collection at CABI and extracted the DNA for sequencing. The resulting genome was compared with the previously published genomes of two commercial Penicillium strains later used in the United States.

The researchers studied two types of genes: those that code for enzymes that the fungus uses to make penicillin; and those that regulate enzymes, for example, by controlling their amount. In both the UK and US strains, the regulatory genes shared the same genetic code, but the US strains had more copies of the regulatory genes, which helped these strains produce more penicillin.

However, the genes encoding penicillin-producing enzymes differed between the strains isolated in the UK and the USA. The researchers say this shows that wild Penicilliums in the UK and US have evolved naturally to produce slightly different versions of these enzymes.

Molds like Penicillium produce antibiotics to fight microbes and are forced to evolve as microbes develop new defenses as well. The UK and US strains likely evolved differently in order to adapt to local microbes.