Secondary Metabolites of Onygenales Fungi Exemplified by Aioliomyces pyridodomos

Abstract

Fungi from Order Onygenales include human pathogens. Although secondary metabolites are critical for pathogenic interactions, relatively little is known about Onygenales compounds. Here, we use chemical and genetic methods on Aioliomyces pyridodomos, the first representative of a candidate new family within Onygenales. We isolated 14 new bioactive metabolites, nine of which are first disclosed here. Thirty-two specialized metabolite biosynthetic gene clusters (BGCs) were identified. BGCs were correlated to some of the new compounds by heterologous expression of biosynthetic genes. Some of the compounds were found after one year of fermentation. By comparing BGCs from A. pyridodomos with those from 68 previously sequenced Onygenales fungi, we delineate a large biosynthetic potential. Most of these biosynthetic pathways are specific to Onygenales fungi and have not been found elsewhere. Family-level specificity and conservation of biosynthetic gene content is evident within Onygenales. Identification of these compounds may be important to understanding pathogenic interactions.

Secondary Metabolism in the Gill Microbiota of Shipworms (Teredinidae) as Revealed by Comparison of Metagenomes and Nearly Complete Symbiont Genomes

“…From the predictions, only the BGCs for PKSs, NRPSs, siderophores, terpenes, homoserine lactones, and thiopeptides (as well as combinations of these biosynthetic enzyme families) were included in the succeeding analyses. An all-versus-all comparison of these BGCs was performed using Multi-GeneBlast (v1.1.14) (32) and a previously reported protocol (65). The bidirectional MultiGeneBlast BGC-to-BGC hits were considered to be reliable.…”

Onygenaleosides A–F, 6/5 Bicyclic Ring Skeleton Triterpene Glycosides with Insecticidal Activity from Onygenales sp. YX1425

“…The HRESIMS data indicated that the molecular formula of onygenaleoside D (4) was C 48 H 82 N 2 O 15 . In a comparison of the NMR data of 4 (Table 2) with 3 (Table 1), the 1 H and 13 Onygenaleoside E ( 5) was obtained as a white powder and afforded the molecular formula C 38 H 65 NO 10 based on its HRESIMS data. A comparison of the molecular weight and NMR data (Table 1 and Table 2 In addition to the six new compounds described above, another two known compounds were identified as malbrancheoside A (7) and malbrancheoside C (8).…”

“…11 Furthermore, these fungi have been found to be taxonomically close to human and animal pathogenic fungi. 12 Previous chemical investigations on the fungi of the family Onygenaceae have led to the isolation of polycyclic ether terpenoids, together with polyketides, 13 lignans, 14 and sesquiterpenes. 15 To further mine bioactive natural products with novel structures, a systematic investigation of the fungus Onygenales sp.…”

A Decade of Antifungal Leads from Natural Products: 2010–2019

“…The putative biosynthetic gene cluster was engineered into an Aspergillus nidulans expression host, enabling the isolation of varicidin A (77) with an MIC50 value of 8 μg/mL against C. Extended fermentation (365 days) of a marine-derived strain of Aioliomyces pyridodomos led to the appearance of new metabolites, of which onydecalin C (75) had an MIC of 2 µg/mL against Histoplasma capsulatum [63]. The same strain, in a more conventional fermentation period (25 days), produced aintennol A (76) with an IC 50 of 8 µg/mL against H. capsulatum [64]. Genome mining for potential Diels-Alderase enzymes identified a potential candidate in the genome sequence of Penicillium variabile.…”