The developmental regulator Pcz1 affects the production of secondary metabolites in the filamentous fungus Penicillium roqueforti

Abstract

Penicillium roqueforti is used in the production of several kinds of ripened blue-veined cheeses. In addition, this fungus produces interesting secondary metabolites such as roquefortine C, andrastin A and mycophenolic acid. To date, there is scarce information concerning the regulation of the production of these secondary metabolites. Recently, the gene named pcz1 (Penicillium C6 zinc domain protein 1) was described in P. roqueforti, which encodes for a Zn(II)Cys protein that controls growth and developmental processes in this fungus. However, its effect on secondary metabolism is currently unknown. In this work, we have analyzed how the overexpression and down-regulation of pcz1 affect the production of roquefortine C, andrastin A and mycophenolic acid in P. roqueforti. The three metabolites were drastically reduced in the pcz1 down-regulated strains. However, when pcz1 was overexpressed, only mycophenolic acid was overproduced while, on the contrary, levels of roquefortine C and andrastin A were diminished. Importantly, these results match the expression pattern of key genes involved in the biosynthesis of these metabolites. Taken together, our results suggest that Pcz1 plays a key role in regulating secondary metabolism in the fungus Penicillium roqueforti.

Regulation of Secondary Metabolism in the Penicillium Genus

“…The pcz1 gene ( Penicillium C6 zinc domain protein 1), encoding a Zn(II)2Cys6 protein and controlling the growth and development processes of the fungus, has also been described in P. roqueforti . It was suggested to participate in the physiological processes in this fungus and plays a key role in regulating its secondary metabolism [ 160 , 161 ]. The silencing of pcz1 in P. roqueforti resulted in the downregulation of the brlA , abaA, and wetA genes of the CRP [ 160 ].…”

“…The silencing of pcz1 in P. roqueforti resulted in the downregulation of the brlA , abaA, and wetA genes of the CRP [ 160 ]. In pcz1 downregulated strains, the production of the metabolites roquefortine C, andrastin A, and mycophenolic acid was severely reduced; however, when pcz1 was overexpressed, only mycophenolic acid was overproduced, and levels of roquefortine C and andrastin A were decreased [ 161 ].…”

Secondary metabolites of a marine-derived Penicillium ochrochloron

“…This compound is known to possess antibacterial properties (Li et al, 2012;Qi et al, 2013;Yadav et al, 2014). Andrastin A (3) has been reported from several Penicillium species including P. roqueforti, P. paneum, P. carneum and P. albocoremium (Uchida et al, 1996;Nielsen et al, 2005;Overy et al, 2005;O'Brien et al, 2006;Rojas-Aedo et al, 2018). Andrastins are meroterpenoids known for inhibiting protein farnesyltransferase (Matsuda and Abe, 2016).…”

Biotechnological approaches for the production of designer cheese with improved functionality

“…Roquefortines are secondary metabolites produced by P. roqueforti having an antibacterial property, which belong to the prenylated indole alkaloid family (Hymery, Mounier, & Coton, 2018). Two secondary metabolites, andrastins, and mycophenolic acid, produced by P. roqueforti and other Penicillium species enhance cheese bio‐functionality by their antitumor and immunosuppressant activities (Rojas‐Aedo et al., 2018). Similarly, 37.2% of the mycotoxin content in 89 blue‐veined cheese contained quantifiable amounts of mycophenolic acid (Fontaine et al., 2015).…”