, a Vintage Model with a Cutting-Edge Profile in Biotechnology.

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 (reclassified as ) 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 is a thoroughly studied model for secondary metabolite production and regulation.

Role of Gene in the Filamentous Fungus .

The (suppressor of four kinase) gene has been mainly studied in , where it was shown to be involved in growth and thermal stress resistance. This gene is widely conserved within the phylum . Despite this, to date has not been studied in any filamentous fungus.

Heterotrimeric G protein alpha subunit controls growth, stress response, extracellular protease activity, and cyclopiazonic acid production in Penicillium camemberti.

The fungus Penicillium camemberti is widely used in the ripening of various bloomy-rind cheeses. Several properties of P. camemberti are important in cheese ripening, including conidiation, growth and enzyme production, among others.

The Biosynthetic Gene Cluster for Andrastin A in .

is a filamentous fungus involved in the ripening of several kinds of blue cheeses. In addition, this fungus produces several secondary metabolites, including the meroterpenoid compound andrastin A, a promising antitumoral compound. However, to date the genomic cluster responsible for the biosynthesis of this compound in has not been described.

[Role of G-protein alpha sub-units in the morphogenic processes of filamentous Ascomycota fungi].

The phylum Ascomycota comprises about 75% of all the fungal species described, and includes species of medical, phytosanitary, agricultural, and biotechnological importance. The ability to spread, explore, and colonise new substrates is a feature of critical importance for this group of organisms. In this regard, basic processes such as conidial germination, the extension of hyphae and sporulation, make up the backbone of development in most filamentous fungi.

Identification and Functional Analysis of the Mycophenolic Acid Gene Cluster of Penicillium roqueforti.

The filamentous fungus Penicillium roqueforti is widely known as the ripening agent of blue-veined cheeses. Additionally, this fungus is able to produce several secondary metabolites, including the meroterpenoid compound mycophenolic acid (MPA). Cheeses ripened with P.

Filamentous fungi from extreme environments as a promising source of novel bioactive secondary metabolites.

Natural product search is undergoing resurgence upon the discovery of a huge previously unknown potential for secondary metabolite (SM) production hidden in microbial genomes. This is also the case for filamentous fungi, since their genomes contain a high number of "orphan" SM gene clusters. Recent estimates indicate that only 5% of existing fungal species have been described, thus the potential for the discovery of novel metabolites in fungi is huge.

The pcz1 gene, which encodes a Zn(II)2Cys6 protein, is involved in the control of growth, conidiation, and conidial germination in the filamentous fungus Penicillium roqueforti.

Proteins containing Zn(II)(2)Cys(6) domains are exclusively found in fungi and yeasts. Genes encoding this class of proteins are broadly distributed in fungi, but few of them have been functionally characterized. In this work, we have characterized a gene from the filamentous fungus Penicillium roqueforti that encodes a Zn(II)(2)Cys(6) protein, whose function to date remains unknown.

Direct involvement of the CreA transcription factor in penicillin biosynthesis and expression of the pcbAB gene in Penicillium chrysogenum.

The transcription factor CreA is the main regulator responsible for carbon repression in filamentous fungi. CreA is a wide domain regulator that binds to regulatory elements in the promoters of target genes to repress their transcription. Penicillin biosynthesis and the expression of penicillin biosynthetic genes are subject to carbon repression.

Heterotrimeric Gα protein Pga1 from Penicillium chrysogenum triggers germination in response to carbon sources and affects negatively resistance to different stress conditions.

Heterotrimeric Gα protein Pga1 of Penicillium chrysogenum controls vegetative growth, conidiation and secondary metabolite production. In this work we studied the role of Pga1 in spore germination and resistance to different stress conditions. Strains G203R-T (expressing the dominant inactivating pga1(G203R) allele) and Δpga1 (deleted pga1) showed a delayed and asynchronic germination pattern, and a decrease in the percentage of germination, which occurred in only 70-80% of the total conidia.

Effect of a heterotrimeric G protein alpha subunit on conidia germination, stress response, and roquefortine C production in Penicillium roqueforti.

Heterotrimeric G protein signaling regulates many processes in fungi, such as development, pathogenicity, and secondary metabolite biosynthesis. For example, the Galpha subunit Pga1 from Penicillium chrysogenum regulates conidiation and secondary metabolite production in this fungus. The dominant activating allele, pga1G42R, encoding a constitutively active Pga1 Galpha subunit, was introduced in Penicillium roqueforti by transformation, resulting in a phenotype characterized by low sporulation and slow growth.

The heterotrimeric Galpha protein pga1 regulates biosynthesis of penicillin, chrysogenin and roquefortine in Penicillium chrysogenum.

We have studied the role of the pga1 gene of Penicillium chrysogenum, encoding the alpha subunit of a heterotrimeric G protein, in secondary metabolite production. The dominant activating pga1(G42R) mutation caused an increase in the production of the three secondary metabolites penicillin, the yellow pigment chrysogenin and the mycotoxin roquefortine, whereas the dominant inactivating pga1(G203R) allele and the deletion of the pga1 gene resulted in a decrease of the amount of produced penicillin and roquefortine. Chrysogenin is produced in solid medium as a yellow pigment, and its biosynthesis is clearly enhanced by the presence of the dominant activating pga1(G42R) allele.

Heterotrimeric Galpha protein Pga1 of Penicillium chrysogenum controls conidiation mainly by a cAMP-independent mechanism.

Fungal heterotrimeric G proteins regulate different processes related to development, such as colony growth and asexual sporulation, the main mechanism of propagation in filamentous fungi. To gain insight into the mechanisms controlling growth and differentiation in the industrial penicillin producer Penicillioum chrysogenum, we investigated the role of the heterotrimeric Galpha subunit Pga1 in conidiogenesis. A pga1 deleted strain (Deltapga1) and transformants with constitutively activated (pga1G42R) and inactivated (pga1G203R) Pga1 alpha subunits were obtained.

The pga1 gene of Penicillium chrysogenum NRRL 1951 encodes a heterotrimeric G protein alpha subunit that controls growth and development.

The pga1 gene of Penicillium chrysogenum NRRL 1951 has been cloned and shown to participate in the developmental program of this fungus. It encodes a protein showing a high degree of identity to group I alpha subunits of fungal heterotrimeric G proteins, presenting in its sequence all the distinctive characteristics of this group. Northern analysis revealed that pga1 is highly expressed in a constitutive manner in submerged cultures, while its expression changes during development on solid media cultures; it is higher during vegetative growth and decreases significantly at the time of conidiogenesis.

High efficiency transformation of Penicillium nalgiovense with integrative and autonomously replicating plasmids.

Penicillium nalgiovense is a filamentous fungus that is acquiring increasing biotechnological importance in the food industry due to its widespread use as starter culture for cured and fermented meat products. Strains of P. nalgiovense can be improved by genetic modification to remove the production of penicillin and other potentially hazardous secondary metabolites, to improve its capacity to control the growth of undesirable fungi and bacteria on the meat product, and other factors that contribute to the ripening of the product in order to get safer and better quality foods.