Targeted Discovery of Tetrapeptides and Cyclic Polyketide‐Peptide Hybrids from a Fungal Antagonist of Farming Termites

• Published in: Chembiochem : a European journal of chemical biology Vol. 21; no. 20; pp. 2991 - 2996
• Main Authors: Schalk, Felix, Um, Soohyun, Guo, Huijuan, Kreuzenbeck, Nina B., Görls, Helmar, Beer, Z. Wilhelm, Beemelmanns, Christine
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 15.10.2020; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Bioassays; Biochemistry & Molecular Biology; Biological Products - chemistry; Biological Products - isolation & purification; Chemistry, Medicinal; Crystallography; Crystallography, X-Ray; Drug Discovery; Fungi; Hybrids; Life Sciences & Biomedicine; Mass spectrometry; Mass spectroscopy; Metabolism; metabolomics; Models, Molecular; Molecular Conformation; Molecular structure; Natural products; NMR; nonribosomal peptide synthetase; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; Oligopeptides - isolation & purification; Peptides; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Pharmacology & Pharmacy; Polyketide synthase; polyketide synthases; Polyketides - chemistry; Polyketides - isolation & purification; Science & Technology; Stereoisomerism; symbionts; Termitomyces - chemistry; Two dimensional analysis; natural products; nonribosomal peptide synthetase; polyketide synthases; metabolomics; symbionts; XYLARIA; peptides; PSEUDOXYLARIA; MASS-SPECTROMETRY
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202000331

Herein, we report the targeted isolation and characterization of four linear nonribosomally synthesized tetrapeptides (pseudoxylaramide A–D) and two cyclic nonribosomal peptide synthetase‐polyketide synthase‐derived natural products (xylacremolide A and B) from the termite‐associated stowaway fungus Pseudoxylaria sp. X187. The fungal strain was prioritized for further metabolic analysis based on its taxonomical position and morphological and bioassay data. Metabolic data were dereplicated based on high‐resolution tandem mass spectrometry data and global molecular networking analysis. The structure of all six new natural products was elucidated based on a combination of 1D and 2D NMR analysis, Marfey's analysis and X‐ray crystallography. Chemical treasures of a fungal stowaway: Structural analysis of six new chemical features revealed four linear tetrapeptides and two cyclic NRPS‐polyketide‐derived natural products from the fungal antagonist Pseudoxylaria sp. X187 of fungus‐growing termites.