The Potential of Arctic Pseudogymnoascus Fungi in the Biosynthesis of Natural Products

Abstract

Scarce research into the secondary metabolites of the fungi Pseudogymnoascus spp. has shown a hidden biosynthetic potential for biologically active compounds. This work investigated the biosynthesis of secondary metabolites by two Pseudogymnoascus fungal strains, VKM F-4518 and VKM F-4519, isolated from the surface soil layer of the Kolyma Lowland, Russia, in the Arctic. In these strains, 16-membered trilactone macrolides, (+)-macrosphelides A and B, were identified using 1D and 2D NMR, UHRMS, and optical rotation data. In the fungi of this genus, these metabolites were found for the first time. The studied strains are highly active producers of macrosphelide A, which is being considered as a promising agent for the cure of cancer. Using the antiSMASH secondary metabolite analysis tool, we found that the genome of strain VKM F-4518 contained 32 of the biosynthetic clusters of the secondary metabolite genes (BGC) and that of VKM F-4519 had 17 BGCs. Based on the comparison of the cluster of macrotriolide genes from the fungus Paraphaeosphaeria sporulosa, we found the complete supposed cluster BGCs of macrosphelides in the genomes of two Pseudogymnoascus strains using the BLAST+ program.

Expanding the Toolbox for Genetic Manipulation in Pseudogymnoascus: RNAi-Mediated Silencing and CRISPR/Cas9-Mediated Disruption of a Polyketide Synthase Gene Involved in Red Pigment Production in P. verrucosus

“…Fungi from the genus Pseudogymnoascus exhibit interesting capabilities in their specialized metabolism [15][16][17][18][19][20][21]. To gain a deeper understanding of Pseudogymnoascus' metabolic potential, molecular tools enabling its genetic manipulation are essential.…”

“…Furthermore, the straightforward application of RNAi-mediated gene silencing positions it as a good choice for high-throughput functional genomics screens, enabling the systematic evaluation of gene silencing effects on diverse cellular processes. In this context, the genomic analysis of Pseudogymnoascus underscores the presence of numerous biosynthetic gene clusters [16], thereby rendering RNAi-mediated gene silencing useful for the simultaneous experimental analysis of these genes, aiming to establish associations with the production of their respective metabolites.…”

“…From a biotechnological perspective, numerous studies have demonstrated that extracts derived from diverse strains of Pseudogymnoascus harbor bioactive metabolites with antibacterial, antifungal, trypanocidal, herbicidal, and antitumoral properties [9][10][11][12][13][14]. Furthermore, chemical analyses of Pseudogymnoascus strains have revealed that members of this fungal genus produce different classes of compounds, such as sesquiterpenes [15], macrolides [16], polyketides [17,18], tetrapeptides [19], and various nitrogenous compounds [20,21]. This underscores the potential of Pseudogymnoascus as a prolific source of specialized metabolites.…”