Fleming’s famous mould revisited

British scientists have sequenced the genome of Alexander Fleming’s famous penicillin mould for – surprisingly – the first time, allowing them to compare it with later versions.

And that’s of more than just historical interest.

Writing in the journal Scientific Reports, they reveal that modern UK and US strains they analysed use slightly different methods to produce penicillin, potentially suggesting new routes for industrial production.

Fleming discovered the first antibiotic in 1928 while working at St Mary’s Hospital Medical School, which is now part of Imperial College London (ICL). It was produced by a mould in the genus Penicillium that accidentally started growing in a Petri dish.

There was an element of chance to the new study, too. The research team from ICL, CABI (the Centre for Agriculture and Bioscience International) and the University of Oxford originally just intended to use Fleming’s fungus for different experiments – until they realised that no-one had yet taken a really good look at it.

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Fleming’s original sample. Credit: CABI

Led by Timothy Barraclough, from ICL and Oxford, they re-grew Fleming’s original Penicillium from a frozen sample kept at the culture collection at CABI and extracted the DNA for sequencing.

Although Fleming’s mould was the source of penicillin, industrial production quickly moved to using fungus from mouldy melons in the US. From there, the Penicillium samples were artificially selected for strains that produce higher volumes of penicillin.

The researchers looked in particular at two kinds of genes: those encoding the enzymes that the fungus uses to produce penicillin; and those that regulate the enzymes, for example by controlling how many enzymes are made.

The regulatory genes had the same genetic code in strains from the US and the UK, although those from the US had more copies of the regulatory genes, helping them produce more penicillin.

However, the genes coding for penicillin-producing enzymes differed between the strains isolated in the UK and US. The researchers say this shows that wild Penicillium in the UK and US evolved naturally to produce slightly different versions of these enzymes. The different strains likely evolved differently to adapt to local microbes.

Although the researchers don’t yet know the consequences of the different enzyme sequences for the eventual antibiotic, they say it does raise the intriguing prospect of new ways to modify penicillin production.

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