TY - JOUR

T1 - Secondary metabolite biosynthetic diversity in the fungal family Hypoxylaceae and Xylaria hypoxylon

AU - Kuhnert, E.

AU - Navarro-Muñoz, J. C.

AU - Becker, K.

AU - Stadler, M.

AU - Collemare, J.

AU - Cox, R. J.

N1 - Funding Information: This work was funded by the DFG (Deutsche Forschungsgemeinschaft) priority program “Taxon-Omics: New Approaches for Discovering and Naming Biodiversity” (SPP 1991). The Odo van Vloten foundation is gratefully acknowledged for financial support of JN. The publication of this article was funded by the Open Access Fund of the Leibniz University Hannover .

PY - 2021/6/1

Y1 - 2021/6/1

N2 - To date little is known about the genetic background that drives the production and diversification of secondary metabolites in the Hypoxylaceae. With the recent availability of high-quality genome sequences for 13 representative species and one relative (Xylaria hypoxylon) we attempted to survey the diversity of biosynthetic pathways in these organisms to investigate their true potential as secondary metabolite producers. Manual search strategies based on the accumulated knowledge on biosynthesis in fungi enabled us to identify 783 biosynthetic pathways across 14 studied species, the majority of which were arranged in biosynthetic gene clusters (BGC). The similarity of BGCs was analysed with the BiG-SCAPE engine which organised the BGCs into 375 gene cluster families (GCF). Only ten GCFs were conserved across all of these fungi indicating that speciation is accompanied by changes in secondary metabolism. From the known compounds produced by the family members some can be directly correlated with identified BGCs which is highlighted herein by the azaphilone, dihydroxynaphthalene, tropolone, cytochalasan, terrequinone, terphenyl and brasilane pathways giving insights into the evolution and diversification of those compound classes. Vice versa, products of various BGCs can be predicted through homology analysis with known pathways from other fungi as shown for the identified ergot alkaloid, trigazaphilone, curvupallide, viridicatumtoxin and swainsonine BGCs. However, the majority of BGCs had no obvious links to known products from the Hypoxylaceae or other well-studied biosynthetic pathways from fungi. These findings highlight that the number of known compounds strongly underrepresents the biosynthetic potential in these fungi and that a tremendous number of unidentified secondary metabolites is still hidden. Moreover, with increasing numbers of genomes for further Hypoxylaceae species becoming available, the likelihood of revealing new biosynthetic pathways that encode new, potentially useful compounds will significantly improve. Reaching a better understanding of the biology of these producers, and further development of genetic methods for their manipulation, will be crucial to access their treasures.

AB - To date little is known about the genetic background that drives the production and diversification of secondary metabolites in the Hypoxylaceae. With the recent availability of high-quality genome sequences for 13 representative species and one relative (Xylaria hypoxylon) we attempted to survey the diversity of biosynthetic pathways in these organisms to investigate their true potential as secondary metabolite producers. Manual search strategies based on the accumulated knowledge on biosynthesis in fungi enabled us to identify 783 biosynthetic pathways across 14 studied species, the majority of which were arranged in biosynthetic gene clusters (BGC). The similarity of BGCs was analysed with the BiG-SCAPE engine which organised the BGCs into 375 gene cluster families (GCF). Only ten GCFs were conserved across all of these fungi indicating that speciation is accompanied by changes in secondary metabolism. From the known compounds produced by the family members some can be directly correlated with identified BGCs which is highlighted herein by the azaphilone, dihydroxynaphthalene, tropolone, cytochalasan, terrequinone, terphenyl and brasilane pathways giving insights into the evolution and diversification of those compound classes. Vice versa, products of various BGCs can be predicted through homology analysis with known pathways from other fungi as shown for the identified ergot alkaloid, trigazaphilone, curvupallide, viridicatumtoxin and swainsonine BGCs. However, the majority of BGCs had no obvious links to known products from the Hypoxylaceae or other well-studied biosynthetic pathways from fungi. These findings highlight that the number of known compounds strongly underrepresents the biosynthetic potential in these fungi and that a tremendous number of unidentified secondary metabolites is still hidden. Moreover, with increasing numbers of genomes for further Hypoxylaceae species becoming available, the likelihood of revealing new biosynthetic pathways that encode new, potentially useful compounds will significantly improve. Reaching a better understanding of the biology of these producers, and further development of genetic methods for their manipulation, will be crucial to access their treasures.

KW - Azaphilones

KW - Binaphthalenes

KW - Biosynthesis

KW - Comparative genomics

KW - Metabolomics

KW - Natural products

KW - Xylariales

UR - http://www.scopus.com/inward/record.url?scp=85113704649&partnerID=8YFLogxK

U2 - 10.1016/j.simyco.2021.100118

DO - 10.1016/j.simyco.2021.100118

M3 - Article

AN - SCOPUS:85113704649

VL - 99

JO - Studies in mycology

JF - Studies in mycology

SN - 0166-0616

M1 - 100118

ER -