Molecular networking and computational NMR analyses uncover six polyketide-terpene hybrids from termite-associated Xylaria isolates.
Seoung Rak Lee, Marie Dayras, Janis Fricke, Huijuan Guo, Sven Balluff, Felix Schalk, Jae Sik Yu, Se Yun Jeong, Bernd Morgenstern, Bernard Slippers, Christine Beemelmanns, Ki Hyun Kim
Author Information
Seoung Rak Lee: School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Marie Dayras: Anti-infectives from Microbiota Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Campus E8.1, 66123, Saarbr��cken, Germany. ORCID
Janis Fricke: Chemical Biology of Microbe-Host Interactions Leibniz institute for Natural Product Research and Infection Biology - Hans-Kn��ll-Institute (HKI), Beutenbergstra��e 11a, 07745, Jena, Germany. ORCID
Huijuan Guo: Chemical Biology of Microbe-Host Interactions Leibniz institute for Natural Product Research and Infection Biology - Hans-Kn��ll-Institute (HKI), Beutenbergstra��e 11a, 07745, Jena, Germany.
Sven Balluff: Anti-infectives from Microbiota Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Campus E8.1, 66123, Saarbr��cken, Germany.
Felix Schalk: Chemical Biology of Microbe-Host Interactions Leibniz institute for Natural Product Research and Infection Biology - Hans-Kn��ll-Institute (HKI), Beutenbergstra��e 11a, 07745, Jena, Germany.
Jae Sik Yu: School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Se Yun Jeong: School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Bernard Slippers: Department of Biochemistry, Genetics and Microbiology, Forestry and Agricultural Biotechnology Institute (FABI), University of Pretoria, Pretoria, South Africa.
Christine Beemelmanns: Anti-infectives from Microbiota Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Campus E8.1, 66123, Saarbr��cken, Germany. christine.beemelmanns@helmholtz-hips.de. ORCID
Ki Hyun Kim: School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea. khkim83@skku.edu. ORCID
Fungi constitute the Earth's second most diverse kingdom, however only a small percentage of these have been thoroughly examined and categorized for their secondary metabolites, which still limits our understanding of the ecological chemical and pharmacological potential of fungi. In this study, we explored members of the co-evolved termite-associated fungal genus Xylaria and identified a family of highly oxygenated polyketide-terpene hybrid natural products using an MS/MS molecular networking-based dereplication approach. Overall, we isolated six no yet reported xylasporin derivatives, of which xylasporin A (1) features a rare cyclic-carbonate moiety. Extensive comparative spectrometric (HRMS) and spectroscopic (1D and 2D NMR) studies allowed to determine the relative configuration across the xylasporin family, which was supported by chemical shift calculations of more than 50 stereoisomers and DP4+ probability analyses. The absolute configuration of xylasporin A (1) was also proposed based on TDDFT-ECD calculations. Additionally, we were able to revise the relative and absolute configurations of co-secreted xylacremolide B produced by single x-ray crystallography. Comparative genomic and transcriptomic analysis allowed us to deduce the putative biosynthetic assembly line of xylasporins in the producer strain X802, and could guide future engineering efforts of the biosynthetic pathway.
