Edinburgh Genomics helps GlaxoSmithKline study historic fungal strains used in antibiotic manufacture
Edinburgh Genomics supported a project involving Professor Louise Horsfall, Dr Matt Edmundson and GlaxoSmithKline (GSK) to investigate the genetics of historic fungal strains used for penicillin production.
Large scale production of penicillin began during the second world war, as well as subsequent work to identify bacterial strains with the highest natural production. Strain NRRL 1951 was discovered on a mouldy melon at a local market and became the ancestor of all modern production strains. Descendent strains were produced via mutagenesis with X-rays and UV light resulting in large archives of fungal mutants, some being discarded while others were further developed.
Modern strains produce 500 times the amount of penicillin of NRRL 1951 and 42,000 times that of Fleming’s original 1920s strain. Modern strains have been sequenced but it was impossible to distinguish beneficial, silent or deleterious mutations.
The project involved sequencing selected archived strains and early production strains, followed by comparison of the sequences of genes known to be involved in penicillin production.
Edinburgh Genomics supported the project with advice on genomic DNA purification and PacBio single-molecule long-read sequencing, as high molecular weight DNA and high purity are required for PacBio sequencing and specifically the removal of RNA and extraction contaminants. Genomic sequences were assembled and compared followed by a secondary bioinformatics analysis by Dr Edmundson.
Results were validated in a subsequent metabolomic screen which determined how specific genomic changes affected penicillin production. GSK were quite pleased to discover some of the secrets their strains had been hiding since the 1940s.
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