Penicillium arizonense, a new, genome sequenced fungal species, reveals a high chemical diversity in secreted metabolites

Grijseels, Sietske; Nielsen, Jens; Randelovic, Milica; Nielsen, Jens; Nielsen, Kristian Fog; Workman, Mhairi; Frisvad, Jens Christian

doi:10.1038/srep35112

Cited by 38 publications

(27 citation statements)

References 86 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Structures of mono‐ and dimeric naphtho‐α‐pyrones from P. citreonigrum , A. ochraceus , and T. rubrum ( 1 , 2 ); from A. viridinutans ( 3 , 4 ) and C. cladosporioides ( 3 ); from H. immaculata ( 5 ); and from P. arizonense ( 7 ) …”

Section: Methodsmentioning

confidence: 79%

See 1 more Smart Citation

Diversity in Fungal Intermolecular Phenol Coupling of Polyketides: Regioselective Laccase‐Based Systems

et al. 2019

View full text Add to dashboard Cite

Polyketides form a structurally diverse and pharmaceutically important class of secondary metabolites. Both diversity and biological activity are largely facilitated by post‐polyketide synthase tailoring including methylation, oxidation, reduction, glycosylation, and dimerization. Cytochrome P450 enzymes (CYPs), flavin‐dependent monooxygenases (FMOs), and laccases are known to catalyze phenol coupling in the biosynthesis of polyketide dimers. Polyketide homodimers resulting from enzyme catalysis are often formed in a highly regio‐ and stereoselective manner, in contrast to analogous nonenzymatic dimerization. Although it is known that CYPs and FMOs are capable of selectively generating one of several putative isomers, hitherto described laccases depend on auxiliary proteins to achieve similar selectivity. Herein, regioselective phenol coupling catalyzed by a fungal laccase is demonstrated. The heterologously produced Av‐VirL from Aspergillus viridinutans selectively generated the 6,6′‐homodimer of (R)‐semivioxanthin. Genome analysis is used to show that laccase‐based phenol‐coupling systems are widespread in fungi. Homologues of Av‐VirL were identified in the putative biosynthetic gene clusters of vioxanthin, xanthomegnin, and xanthoepocin, and of the perylenequinones hypocrellin A, elsinochrome A, and cercosporin. These findings show that laccases are capable of selective phenol coupling in the absence of auxiliary proteins.

show abstract

Section: Methodsmentioning

confidence: 79%

“…Dimeric naphtho‐α‐pyrone 7 has been isolated from Penicillium arizonense . Because of the striking structural resemblance of 7 to 2 , we predicted a similar biosynthetic pathway with an analogous set of enzymes (Figure ).…”

Section: Methodsmentioning

confidence: 99%

Diversity in Fungal Intermolecular Phenol Coupling of Polyketides: Regioselective Laccase‐Based Systems

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Several other metabolites with predicted BGCs and previously detected in solid cultivations of the corresponding strains, could not be detected in the submerged cultivations of the same strain. This was the case for yanuthones previously detected in extracts of P. flavigenum grown on agar plates [ 15 ], and fumagillin, pyripyropenes, austalides, and tryptoquivalines, previously detected in extracts of P. arizonense grown on agar plates [ 14 ]. In this context it is interesting that a species like P. arizonense only secreted pseurotin A, despite the large potential for producing a vast number of secondary metabolites.…”

Section: Discussionmentioning

confidence: 87%

“…The recent genome sequencing of ten Penicillium species [ 14 , 15 ] has provided valuable novel insight into the rich diversity in secondary metabolite gene clusters present in these Penicillium species and has in addition, made the species amenable to rational strain improvement. In this study, we analyzed the potential of these ten recently genome sequenced Penicillium species as native producing cell factories.…”

Section: Introductionmentioning

confidence: 99%

Physiological characterization of secondary metabolite producing Penicillium cell factories

Grijseels

Nielsen

et al. 2017

Fungal Biol Biotechnol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Recent sequencing efforts on new Penicillium genomes have provided new insights into the genomic diversity within the genus (Grijseels et al, ; J. C. Nielsen et al, ), and this enables further discovery of the metabolic capabilities of these species. Here, we show how automatic network reconstruction can be applied to reconstruct GEMs of phylogenetically closely related species having limited experimental characterization.…”

Section: Introductionmentioning

confidence: 99%

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

Prigent

Nielsen

Frisvad

et al. 2018

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

Modeling of metabolism at the genome-scale has proved to be an efficient method for explaining the phenotypic traits observed in living organisms. Further, it can be used as a means of predicting the effect of genetic modifications for example, development of microbial cell factories. With the increasing amount of genome sequencing data available, there exists a need to accurately and efficiently generate such genome-scale metabolic models (GEMs) of nonmodel organisms, for which data is sparse. In this study, we present an automatic reconstruction approach applied to 24 Penicillium species, which have potential for production of pharmaceutical secondary metabolites or use in the manufacturing of food products, such as cheeses. The models were based on the MetaCyc database and a previously published Penicillium GEM and gave rise to comprehensive genome-scale metabolic descriptions. The models proved that while central carbon metabolism is highly conserved, secondary metabolic pathways represent the main diversity among species. The automatic reconstruction approach presented in this study can be applied to generate GEMs of other understudied organisms, and the developed GEMs are a useful resource for the study of Penicillium metabolism, for example, for the scope of developing novel cell factories.

show abstract

Penicillium arizonense, a new, genome sequenced fungal species, reveals a high chemical diversity in secreted metabolites

Cited by 38 publications

References 86 publications

Diversity in Fungal Intermolecular Phenol Coupling of Polyketides: Regioselective Laccase‐Based Systems

Diversity in Fungal Intermolecular Phenol Coupling of Polyketides: Regioselective Laccase‐Based Systems

Physiological characterization of secondary metabolite producing Penicillium cell factories

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

Contact Info

Product

Resources

About