Pseudoxylallemycins A–F, Cyclic Tetrapeptides with Rare Allenyl Modifications Isolated from Pseudoxylaria sp. X802: A Competitor of Fungus-Growing Termite Cultivars

Abstract

Based on fungus-fungus pairing assays and HRMS-based dereplication strategy, six new cyclic tetrapeptides, pseudoxylallemycins A-F (1-6), were isolated from the termite-associated fungus Pseudoxylaria sp. X802. Structures were characterized using NMR spectroscopy, HRMS, and Marfey's reaction. Pseudoxylallemycins B-D (2-4) possess a rare and chemically accessible allene moiety amenable for synthetic modifications, and derivatives A-D showed antimicrobial activity against Gram-negative human-pathogenic Pseudomonas aeruginosa and antiproliferative activity against human umbilical vein endothelial cells and K-562 cell lines.

Precursor‐Directed Diversification of Cyclic Tetrapeptidic Pseudoxylallemycins

“…Subsequently, we evaluated the cytotoxicity, antibacterial, and antiparasitic activities of our extended compound library. Similar to previous reports, pseudoxylallemycins G1–M3 ( 23 – 31 , 38 – 43 , and 47 – 52 ) showed moderate inhibitory activity against Pseudomonas aeruginosa (minimal inhibitory concentration, MIC ≈12.5 μg mL −1 ) and towards human umbilical vein endothelial cells (HUVECs) independently of the introduced side chain modifications (GI 50 =9–15 μg mL −1 ; Table S33). As part of our bioactivity screening efforts, pseudoxylallemycins A–C ( 1 – 3 ) were also subjected to antiparasitic activity assays.…”

“…Again, X802 was cultivated for 4 weeks until the agar was fully covered with mycelium. Agar pieces were extracted with MeOH (2×), and the concentrated extract was purified by using preactivated SPE‐C 18 cartridges . Subsequent Sephadex LH20 and semipreparative HPLC purification resulted in the isolation of the corresponding pseudoxylallemycins.…”

“…We recently reported the isolation of antibacterial tetracyclic peptides named pseudoxylallemycins A–F ( 1 – 6 ) from the stowaway fungus Pseudoxylaria sp. X802 of fungus‐growing termites (Scheme ) …”

Genomics‐Driven Discovery of a Symbiont‐Specific Cyclopeptide from Bacteria Residing in the Rice Seedling Blight Fungus

“…[31][32][33][34][35][36][37][38][39] Therefore, we monitored all available Burkholderia endosymbionts of R. microsporus strains from highly diverse geographic regions aroundt he globe [5] for heptarhizin production( Figure 3A and B). [31][32][33][34][35][36][37][38][39] Therefore, we monitored all available Burkholderia endosymbionts of R. microsporus strains from highly diverse geographic regions aroundt he globe [5] for heptarhizin production( Figure 3A and B).…”

Total Synthesis of Allene-Containing Cyclic Tetrapeptide Pseudoxylallemycin C

“…Accordingly, development of methodology to access these remarkable scaffolds is of continued interest. The pseudoxylallemycin family of CTPs ( Figure 1) were first reported in 2016 6 and have since been the subject of chemical synthesis 7,8 and bio-synthetic 9 studies. We recently reported the total synthesis of pseudoxylallemycin A (1), 7 Template for SYNLETT © Thieme Stuttgart • New York 2020-10-05 page 2 of 4…”