New and more effective strains of the fungus used to produce penicillin could be developed after a team of international scientists unearthed the secret sex life of Sir Alexander Fleming's fungus Penicillium chrysogenum (P. chrysogenum).
The scientists from The University of Nottingham, Ruhr-University Bochum, The University of Göttingen, and Sandoz GmbH have announced a major breakthrough in our understanding of the sex life of the fungus P. chrysogenum. Their research looks sets to lead to the introduction of new and more effective strains of the world's first antibiotic agent and has been published online in the leading academic journal Proceedings of the National Academy of Sciences USA (PNAS).
Penicillium chrysogenum is a filamentous fungus of major medical and historical importance. It is the original and present-day industrial source of the antibiotic penicillin. For over 100 years the fungus has been thought to be asexual, but the researchers have discovered a method to entice the fungus into sexual reproduction. They've demonstrated that sexual crosses can be used to develop new strains with improved industrial characteristics.
Dr Paul Dyer, an expert in the sexual development and genetics of filamentous fungi in the School of Biology at Nottingham, said: "We now have a valuable tool for creating new strains of P. chrysogenum with increased penicillin production. This will make it cheaper to produce penicillin, as using more efficient strains will lower production costs. In the future, it is hoped our method can be applied to other fungi that produce antibiotics."
Our method might also be used to help discover hidden sexual cycles in other economically important fungi that are assumed to be exclusively asexual."
The development of penicillin
Penicillium chrysogenum first came to attention in 1928 when Sir Alexander Fleming made the fortuitous discovery that a Penicillium mold, which had contaminated a bacterial culture, was able to inhibit the growth of nearby bacteria by releasing penicillin into its surroundings. Over 10 years later two scientists, Ernst Chain and Howard Florey, were the first to grow the fungus in large quantities to generate enough penicillin to treat patients. These events heralded the start of the antibiotic era, which has been one of the most important advances in medicine. Fleming, Chain, and Florey later shared the Nobel Prize in physiology/medicine. Since then it has only been possible to develop strains of P. chrysogenum with elevated production of penicillin by conventional mutagenesis.
The researchers found that sexual reproduction could be induced in P. chrysogenum when strains were mated in the dark on oatmeal with a vitamin supplement. They demonstrated that the sexual cycle could be used for strain development purposes by producing offspring with new combinations of important biotechnological properties for penicillin production, such as the removal of chrysogenin, a contaminating substance produced by the fungus. Furthermore, the team discovered that mating-type genes, which control sex in fungi, have additional roles regulating other developmental processes of biotechnological relevance.
Inducing sex in celibate fungi
Fungi are used to produce many important pharmaceutical products including statins and antibiotics, and most species involved have long been considered to be asexual. But the present findings suggest that sexual reproduction could be triggered in other supposedly asexual fungi if the mating-type genes and correct growth conditions can be identified.
The research was led by Professors Ulrich Kück and Stefanie Pöggeler from Germany, Dr Paul Dyer from the UK, and scientists from Sandoz GmbH, a world leader in the industrial production of penicillin and other pharmaceuticals. Other major contributors were PhD student Julia Böhm (Bochum) and postdoctoral research fellow Dr Céline O'Gorman (Nottingham). The work was funded by The Christian Doppler Society (Austria) and The Wellcome Trust (UK).
J. Böhm, B. Hoff, C.M. O'Gorman, S. Wolfers, V. Klix, D. Binger, I. Zadra, H. Kürnsteiner, S. Pöggeler, P.S. Dyer, U. Kück (2013). Sexual reproduction and mating-type-mediated strain development in the penicillin-producing fungus Penicillium chrysogenum. Proceedings of the National Academy of Sciences of the United States of America, DOI: 10.1073/pnas.1217943110.