Original Article Impact of Velvet Complex on Transcriptome and Penicillin G Production in Glucose-Limited Chemostat Cultures of a b-Lactam High-Producing

The multicomponent global regulator Velvet complex has been identified as a key regulator of secondary metabolite production in Aspergillus and Penicillium species. Previous work indicated a massive impact of PcvelA and PclaeA deletions on penicillin production in prolonged batch cultures of P. chrysogenum, as well as sub-stantial changes in transcriptome. The present study investigated the impact of these mutations on product formation and genome-wide transcript profiles under glucose-limited aerobic conditions, relevant for industrial production of b-lactams. Predicted amino acid sequences of PcVelA and PcLaeA in this strain were identical to those in its ancestor Wisconsin54-1255. Controls were performed to rule out transformation-associated loss of penicillin-biosynthesis clusters. The correct PcvelA and PclaeA deletion strains revealed a small reduction of penicillin G productivity relative to the reference strain, which is a much smaller reduction than previously reported for prolonged batch cultures of similar P. chrysogenum mutants. Chemostat-based transcriptome analysis yielded only 23 genes with a consistent differential response in the PcvelAD and PclaeAD mutants when grown in the absence of the penicillin G side-chain precursor phenylacetic acid. Eleven of these genes belonged to two small gene clusters, one of which contained a gene with high homology to the aristolochene synthase. These results provide a clear caveat that the impact of the Velvet complex on secondary metabolism in fila