Physiological characterization of secondary metabolite producing Penicillium cell factories

Abstract

Background Penicillium species are important producers of bioactive secondary metabolites. However, the immense diversity of the fungal kingdom is only scarcely represented in industrial bioprocesses and the upscaling of compound production remains a costly and labor intensive challenge. In order to facilitate the development of novel secondary metabolite producing processes, two routes are typically explored: optimization of the native producer or transferring the enzymatic pathway into a heterologous host. Recent genome sequencing of ten Penicillium species showed the vast amount of secondary metabolite gene clusters present in their genomes, and makes them accessible for rational strain improvement. In this study, we aimed to characterize the potential of these ten Penicillium species as native producing cell factories by testing their growth performance and secondary metabolite production in submerged cultivations.ResultsCultivation of the fungal species in controlled submerged bioreactors showed that the ten wild type Penicillium species had promising, highly reproducible growth characteristics in two different media. Analysis of the secondary metabolite production using liquid chromatography coupled with high resolution mass spectrometry proved that the species produced a broad range of secondary metabolites, at different stages of the fermentations. Metabolite profiling for identification of the known compounds resulted in identification of 34 metabolites; which included several with bioactive properties such as antibacterial, antifungal and anti-cancer activities. Additionally, several novel species–metabolite relationships were found.ConclusionsThis study demonstrates that the fermentation characteristics and the highly reproducible performance in bioreactors of ten recently genome sequenced Penicillium species should be considered as very encouraging for the application of native hosts for production via submerged fermentation. The results are particularly promising for the potential development of the ten analysed Penicillium species for production of novel bioactive compounds via submerged fermentations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40694-017-0036-z) contains supplementary material, which is available to authorized users.

Reconstruction of 24 Penicillium genome‐scale metabolic models shows diversity based on their secondary metabolism

“…By constraining the maximum specific oxygen uptake rate to 10 mmol·gDW −1 ·hr −1 and the maximum specific glucose uptake rate to 5 mmol·gDW −1 ·hr −1 ; the maximum specific growth rate was in the range 0.305–0.323 hr −1 . Similar specific growth rates have been experimentally determined measured for 10 of the 24 species where they range between 0.19 and 0.24 hr −1 in defined media with glucose as the sole carbon source (Grijseels et al, ).…”

“…They correspond to growth in a minimal media and with only a few cofactors. This minimal growth medium was designed based on experimental observations (Grijseels et al, ). For each of the 24 GEMs, a biomass function was constructed based on the biomass function of P. rubens , as described previously (Agren et al, ).…”

“…Among the large number of identified Penicillium species, 354 species were identified in 2014 (Visagie et al, ), and with the increasing availability of sequenced genomes, there has been much interest in evaluation of whether other species in this genus could be exploited for industrial production of fungal secondary metabolites (J. C. Nielsen & Nielsen, ). Wild‐type Penicillium species have shown promising phenotypes as industrial secondary metabolite–producing cell factories in bioreactor fermentations (Grijseels et al, ). However, with genome‐sequencing becoming easier, it would be valuable to perform automatic reconstruction of GEMs that include secondary metabolism, as this would allow for quick evaluation of the metabolic capabilities of different species.…”

Cultivable marine fungi from the Arctic Archipelago of Svalbard and their antibacterial activity

“…The study showed that Penicillium species have highly variable secondary metabolite production, ranging from producing 4 to 34 different identified secondary metabolites. These metabolites were often species specific, among the identified metabolites only six were shared between some of the species, none were shared between all (Grijseels et al 2017 ).…”

Date Palm Trees Root-Derived Endophytes as Fungal Cell Factories for Diverse Bioactive Metabolites

“…Recently, fungal cell factories are attracting significant interest due to their biotechnological potential [ 1 , 18 , 19 , 20 ]. The strategy has been widely applied to primary metabolism towards the production of enzymes or their derived metabolites.…”