Asexual Cephalosporin C Producer Acremonium chrysogenum Carries a Functional Mating Type Locus

Abstract

Acremonium chrysogenum, the fungal producer of the pharmaceutically relevant ␤-lactam antibiotic cephalosporin C, is classified as asexual because no direct observation of mating or meiosis has yet been reported. To assess the potential of A. chrysogenum for sexual reproduction, we screened an expressed sequence tag library from A. chrysogenum for the expression of mating type (MAT) genes, which are the key regulators of sexual reproduction. We identified two putative mating type genes that are homologues of the ␣-box domain gene, MAT1-1-1 and MAT1-1-2, encoding an HPG domain protein defined by the presence of the three invariant amino acids histidine, proline, and glycine. In addition, cDNAs encoding a putative pheromone receptor and pheromone-processing enzymes, as well as components of a pheromone response pathway, were found. Moreover, the entire A. chrysogenum MAT1-1 (AcMAT1-1) gene and regions flanking the MAT region were obtained from a genomic cosmid library, and sequence analysis revealed that in addition to AcMAT1-1-1 and AcMAT1-1-2, the AcMAT1-1 locus comprises a third mating type gene, AcMAT1-1-3, encoding a high-mobility-group domain protein. The ␣-box domain sequence of AcMAT1-1-1 was used to determine the phylogenetic relationships of A. chrysogenum to other ascomycetes. To determine the functionality of the AcMAT1-1 locus, the entire MAT locus was transferred into a MAT deletion strain of the heterothallic ascomycete Podospora anserina (the Pa⌬MAT strain). After fertilization with a P. anserina MAT1-2 (MAT ؉ ) strain, the corresponding transformants developed fruiting bodies with mature ascospores. Thus, the results of our functional analysis of the AcMAT1-1 locus provide strong evidence to hypothesize a sexual cycle in A. chrysogenum.

Presence and Functionality of Mating Type Genes in the Supposedly Asexual Filamentous Fungus Aspergillus oryzae

“…There have been similar reports of the presence of both MAT1-1 and MAT1-2 isolates in populations of other "asexual" pezizomycete fungi, including Alternaria species (2), Aspergillus species (49,58), Rhynchosporium species (37,66), Cercospora species (21), Coccidioides species (18,40), and Penicillium chrysogenum (23,24). The only exception has been the asexual species Acremonium chrysogenum, used to produce cephalosporin, for which only the MAT1-1 genotype could be found in a preliminary survey (55).…”

Sex in Penicillium: Combined phylogenetic and experimental approaches

“…Finally, apparently functional mating type genes (i.e. genes that define mating compatibility in fungi) have recently been identified and characterized in several species with no sexual cycle described, such as A. oryzae (Galagan et al, 2005), and recently in Penicillium chrysogenum and Acremonium chrysogenum Pöggeler et al, 2008). Other fungal species shown to be truly clonal from a population genetic standpoint, such as Penicillium marneffei, also present mating type genes, suggesting that sex has been lost recently (Woo et al, 2006;Fisher, 2007).…”

The autophagy-related gene Acatg1 is involved in conidiation and cephalosporin production in Acremonium chrysogenum

“…So far, cephalosporin has been widely used in treatment of bacterial infectious diseases and is one of the major biotechnological products (Poggeler et al, 2008). In recent years, considerable progress has been made in understanding cephalosporin biosynthesis in A. chrysogenum (Dreyer et al, 2007;Long et al, 2013;Lopez-Calleja et al, 2012;Martin et al, 2010Martin et al, , 2012Schmitt et al, 2004aSchmitt et al, , 2004bSchmitt et al, , 2004cTeijeira et al, 2009).…”