AUTHOR=Rojas-Aedo Juan F. , Gil-Durán Carlos , Del-Cid Abdiel , Valdés Natalia , Álamos Pamela , Vaca Inmaculada , García-Rico Ramón O. , Levicán Gloria , Tello Mario , Chávez Renato 

TITLE=The Biosynthetic Gene Cluster for Andrastin A in Penicillium roqueforti

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00813

DOI=10.3389/fmicb.2017.00813

ISSN=1664-302X

ABSTRACT=<p><italic>Penicillium roqueforti</italic> 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 <italic>P. roqueforti</italic> has not been described. In this work, we have sequenced and annotated a genomic region of approximately 29.4 kbp (named the <italic>adr</italic> gene cluster) that is involved in the biosynthesis of andrastin A in <italic>P. roqueforti</italic>. This region contains ten genes, named <italic>adrA, adrC, adrD, adrE, adrF, adrG, adrH, adrI, adrJ</italic> and <italic>adrK</italic>. Interestingly, the <italic>adrB</italic> gene previously found in the <italic>adr</italic> cluster from <italic>P. chrysogenum</italic>, was found as a residual pseudogene in the <italic>adr</italic> cluster from <italic>P. roqueforti</italic>. RNA-mediated gene silencing of each of the ten genes resulted in significant reductions in andrastin A production, confirming that all of them are involved in the biosynthesis of this compound. Of particular interest was the <italic>adrC</italic> gene, encoding for a major facilitator superfamily transporter. According to our results, this gene is required for the production of andrastin A but does not have any role in its secretion to the extracellular medium. The identification of the <italic>adr</italic> cluster in <italic>P. roqueforti</italic> will be important to understand the molecular basis of the production of andrastin A, and for the obtainment of strains of <italic>P. roqueforti</italic> overproducing andrastin A that might be of interest for the cheese industry.</p>