Insight into the Genome of Diverse Penicillium chrysogenum Strains: Specific Genes, Cluster Duplications and DNA Fragment Translocations

Abstract

Background: There are eighteen species within the Penicillium genus section chrysogena, including the original penicillin producers Penicillium notatum (Fleming strain) and Penicillium chrysogenum NRRL 1951. Other wild type isolates of the Penicillium genus are relevant for the production of useful proteins and primary or secondary metabolites. The aim of this article is to characterize strain specific genes and those genes which are involved in secondary metabolite biosynthesis, particularly the mutations that have been introduced during the β-lactams strain improvement programs. Results: The available genomes of several classical and novel P. chrysogenum strains have been compared. The first genome sequenced was that of the reference strain P. chrysogenum Wis54-1255, which derives from the wild type P. chrysogenum NRRL 1951; its genome size is 32.19 Mb and it encodes 12,943 proteins. Four chromosomes were resolved in P. chrysogenum and P. notatum by pulse field gel electrophoresis. The genomes of three industrial strains have a similar size but contain gene duplications and truncations; the penicillin gene cluster copy number ranges from one in the wild type to twelve in the P. chrysogenum ASP-E1 industrial strain and is organized in head to tail tandem repeats. The genomes of two new strains, P. chrysogenum KF-25, a producer of antifungal proteins isolated from a soil sample, and P. chrysogenum HKF2, a strain with carbohydrate-converting activities isolated from a sludge treatment plant, showed strain specific genes. Conclusions: The overall comparison of all available P. chrysogenum genomes indicates that there are a significant number of strain-specific genes, mutations of structural and regulatory genes, gene cluster duplications and DNA fragment translocations. This information provides important leads to improve the biosynthesis of enzymes, antifungal agents, prebiotics or different types of secondary metabolites.

The Penicillium chrysogenum Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen Candida albicans

“…In silico structural prediction was done based on the hypothetical protein annotated as Pc21g12970 (National Center for Biotechnology Information (NCBI), accession number XP_002568323) in Penicillium rubens Wisconsin 54-1255, which is a descendent of P. chrysogenum Q176 [14,15]. Full-length protein aa sequence was submitted to the I-Tasser server [17] for prediction of the secondary and tertiary protein structure.…”

“…The aim of this study was to characterize the antimicrobial protein PAFC of P. chrysogenum strain Q176, a descendant of the original penicillin producer strain NRRL1951 and the ancestor of the Wis54-1255 strain whose genome was sequenced [14,15]. For simplicity, we refer in the following to P. chrysogenum Q176 as P. chrysogenum.…”

The Confusion in Renaming Species: Penicillium chrysogenum and Penicillium rubens

“…We foresee that in the international literature, penicillin-producing strains will continue to be called Penicillium chrysogenum , since all industrial strains can be traced back to a common ancestor, the wild-type strain NRRL 1951 (CBS 307.48), as was outlined in previous papers ( 8 , 11 ).…”

Penicillium chrysogenum, a Vintage Model with a Cutting-Edge Profile in Biotechnology

“…In addition, transcriptomic, proteomic, and metabolomic studies have been performed trying to elucidate the metabolic changes underwent by industrial strains that led to the high productivity they possess [ 20 , 21 , 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Some recent reviews summarize and make a comprehensive account of the main results obtained in these studies [ 25 , 36 , 37 , 38 , 39 , 40 ].…”

“…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 CSI programs to increase penicillin productivity (reviewed in [ 25 , 36 , 37 , 38 , 39 , 40 ]). As a quick summary, we can mention that, in high-producing strains, there is an upregulation of proteins involved in synthesis of NADPH and cysteine as well as in ATP-producing carbon catabolism, the three compounds having proven essential for high levels of penicillin production [ 61 , 62 ].…”