Transfer of Secondary Metabolite Gene Clusters: Assembly and Reorganization of the β-Lactam Gene Cluster from Bacteria to Fungi and Arthropods

Martı́n, Juan F.; Liras, Paloma

doi:10.1007/978-3-030-21862-1_14

Cited by 4 publications

(12 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of introns in the pcbAB and pcbC genes, their high percentage of G + C content, similar to organisms such as Actinobacteria, and the phylogenetic analyses of the IPNS proteins strongly support the directionality of the transfer from bacteria to fungi [ 151 ]. However, the number of HGTs and the possibility that lateral gene transfers (LGT) between fungi also occurred during the formation of the current penicillin gene cluster is a matter of discussion.…”

Section: Where’d You Get Those Genes?mentioning

confidence: 99%

“…According to the second hypothesis, in one event, all the genes necessary to produce a cephalosporin ring would have been transferred from Streptomyces to an ancestor of Acremonium chrysogenum , and in the other transfer event, only the ACVS and IPNS genes would have been transferred from Streptomyces to a penicillin producer ancestor. More recently, Martín and Liras [ 151 ] proposed a hypothesis that integrated all the evidence available to date. According to this hypothesis, there was only one HGT event of the cephalosporin biosynthetic cluster from bacteria to fungi, specifically to an ancestor of Pochonia chlamydosporia (order Hypocreales).…”

Section: Where’d You Get Those Genes?mentioning

confidence: 99%

“…The analysis of the cephalosporin gene cluster in different cephalosporin producing fungi indicates that P. chlamydosporia has conserved the genes pcbAB , pcbC , and cefEF clustered together, while in A. chrysogenum , the cefEF gene split from the cluster to a new location in another chromosome [ 46 ]. Regarding the origin of the penicillin cluster, Martin and Liras [ 151 ] proposed that there was an LGT event of the pcbAB and pcbC genes from Hypocreales to Eurotiales after the split of these two orders, a hypothesis based on the phylogenetic distance between Hypocreales and Eurotiales and the absence of the genes specific for cephalosporin production in Eurotiales.…”

Section: Where’d You Get Those Genes?mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Section: Where’d You Get Those Genes?mentioning

confidence: 99%

Section: Where’d You Get Those Genes?mentioning

confidence: 99%

Section: Where’d You Get Those Genes?mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2022

View full text Add to dashboard Cite

show abstract

“…This indicates that these genes are strain-specific genes [3]. Some of them may correspond to secondary metabolites gene clusters that may have been acquired or lost by horizontal gene transfer [8]. Some other P. chrysogenum Wis54-1255 strain-specific genes correspond to proteins of unknown function which frequently are found in repetitive sequences, or to virus or transposons-related sequences [25,46].…”

Section: Genomes Of Other Wild Type P Chrysogenum Strainsmentioning

confidence: 99%

“…Penicillins are modified non-ribosomal synthesized peptides that are condensed by oxidative cyclization reactions forming the penam nucleus [4,5]. Penicillin and other β-lactams are produced by several species of ascomycetes fungi [6][7][8], although they are an infrequent type of secondary metabolites; gene clusters for polyketide and lineal or cyclic non-ribosomal peptides, other than β-lactams, are more frequent in the fungal genomes. The first studies of the antibacterial activity of penicillin were made with the compound obtained from the wild type P. notatum [3].…”

Section: Introduction: Penicillium Chrysogenum As a Platform For The Biotechnology Of Fungal Productsmentioning

confidence: 99%

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

Martín

2020

IJMS

View full text Add to dashboard Cite

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.

show abstract

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Zhgun

2023

Fermentation

View full text Add to dashboard Cite

The natural fermentation of antibiotics, along with semi-synthetic and synthetic approaches, is one of the most important methods for their production. The majority of the antibiotic market comes from the fermentation of high-yielding (HY) fungal strains. These strains have been obtained since the 1950s from wild-type (WT) isolates as a result of classical strain improvement (CSI) programs primarily involving multi-round random mutagenesis and screening. However, the molecular basis leading to high-yield production was unknown. In recent years, due to the application of multiomic approaches, key changes that occur in CSI programs, with WT strains that become HY industrial producers of a particular antibiotic, have begun to be understood. It becomes obvious that, during CSI, certain universal events are selected, which lead both to a direct increase in the production of the target metabolite and affect other vital processes of the cell (side mutations). These key events include: the upregulation of the target biosynthetic gene cluster (BGC), changes in the system of global regulation, disruption of alternative BGCs, the rearrangement of energy fluxes in favor of the target SM (secondary metabolite), changes in the regulation of the response to stress, and the redirection of primary metabolic pathways to obtain more precursors for target production. This knowledge opens up the possibility of both introducing targeted changes using genetic engineering methods when creating new producers and increasing the production of CSI strains as a result of fermentation with low-molecular compounds, targeted to compensate for the effects of side mutations.

show abstract

Transfer of Secondary Metabolite Gene Clusters: Assembly and Reorganization of the β-Lactam Gene Cluster from Bacteria to Fungi and Arthropods

Cited by 4 publications

References 83 publications

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

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

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

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers

Contact Info

Product

Resources

About