Bioprocess-related, morphological and bioinformatic perspectives on the biosynthesis of secondary metabolites produced by Penicillium solitum

Abstract

Abstract The qualitative and quantitative analysis of the secondary metabolic repertoire of Penicillium solitum CBS 288.36 in submerged and surface liquid cultures was performed with the use of UPLC–MS. The examination of culture filtrates led to the identification of nine previously described molecules (compactin, 4a,5-dihydrocompactin, 3α-hydroxy-3,5-dihydro ML-236C, ML-236A, cyclopenin, cyclopenol, cyclopeptin, dehydrocyclopeptin and atlantinone A). The production of secondary metabolites was observed to be inhibited under submerged conditions in the standard growth media. In order to induce the underlying pathways in the submerged cultures, several cultivation-related strategies were applied, including the supplementation with glycerol, mannitol, calcium chloride or rapeseed oil, adjusting the initial concentration of nitrogen sources and subjecting the growing mycelia to various aeration intensities and mechanical stress caused by the impeller in a stirred tank bioreactor. The correlation between compactin concentration, dissolved oxygen level and mycelial morphology was observed. On the basis of sequence similarity analysis, the genes involved in the biosynthesis of benzodiazepine alkaloids and meroterpenoids were detected in the genomes of several P. solitum strains. This work describes a novel attempt to quantitatively analyse the metabolic spectrum of P. solitum in shake flask and stirred tank bioreactor cultures with the use of a diverse set of media.