Abstract
The discovery of penicillin entailed a decisive breakthrough in medicine. No other medical advance has ever had the same impact in the clinical practise. The fungus Penicillium chrysogenum (reclassified as P. rubens) has been used for industrial production of penicillin ever since the forties of the past century; industrial biotechnology developed hand in hand with it, and currently P. chrysogenum is a thoroughly studied model for secondary metabolite production and regulation. In addition to its role as penicillin producer, recent synthetic biology advances have put P. chrysogenum on the path to become a cell factory for the production of metabolites with biotechnological interest. In this review, we tell the history of P. chrysogenum, from the discovery of penicillin and the first isolation of strains with high production capacity to the most recent research advances with the fungus. We will describe how classical strain improvement programs achieved the goal of increasing production and how the development of different molecular tools allowed further improvements. The discovery of the penicillin gene cluster, the origin of the penicillin genes, the regulation of penicillin production, and a compilation of other P. chrysogenum secondary metabolites will also be covered and updated in this work.
Highlights
Penicillium chrysogenum was not the first fungus ever to be used in an industrial process, this honor corresponds to Aspergillus niger, which, in 1919, was first put to produce a chemical for the benefit of people, citric acid [1]
Amplification of the penicillin gene cluster, chromosomal rearrangement involving regions with presence of penicillin-related genes, and point mutations in genes involved in global regulation (Velvet complex) and secondary metabolite pathways are the main genetic changes found in high-producing strains detected by genetic and genomic analysis
Other OMICs methodologies, such as proteomics and transcriptomics, allow more functional approaches to elucidate how the metabolism and other cellular processes have been affected during classical strain improvement (CSI) programs to increase penicillin productivity
Summary
Penicillium chrysogenum was not the first fungus ever to be used in an industrial process, this honor corresponds to Aspergillus niger, which, in 1919, was first put to produce a chemical for the benefit of people, citric acid [1]. We intend to tell a brief history of P. chrysogenum, focusing on aspects such as the historical development of improved strains, genomic studies of high-producing strains, the penicillin biosynthetic pathway and its regulation, the origin of the penicillin biosynthetic genes, other secondary metabolites produced by P. chrysogenum, metabolic engineering approaches, and synthetic biology developments. We will update these topics, linking the historical developments with the current state-of-the-art in penicillin and P. chrysogenum research, trying to give an overall comprehensive account of all of them
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