Discovery of Cymopolyphenols A–F From a Marine Mesophotic Zone Aaptos Sponge-Associated Fungus Cymostachys sp. NBUF082

• Main Authors: Tingting Wang, Jing Zhou, Jiabin Zou, Yutong Shi, Wenli Zhou, Peng Shao, Tianze Yu, Wei Cui, Xiaohui Li, Xingxin Wu, Jing Ye, Xiaojun Yan, C. Benjamin Naman, J. Enrico H. Lazaro, Shan He
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-02-01
• Series: Frontiers in Microbiology
• Subjects: mesophotic coral ecosystems; twilight zone; sponges; fungi; sponge-associated fungi; natural products
• Online Access: https://www.frontiersin.org/articles/10.3389/fmicb.2021.638610/full

Mesophotic coral ecosystems (MCEs) have complex but understudied biodiversity, especially for natural products discovery. Untargeted metabolomics research on 80 extracts prepared from marine sponge-associated fungi, half from shallow reefs (<30 m) and half from MCEs (30–150 m), facilitated prioritization for further study a Cymostachys fungus from a 103 m deep Aaptos sponge. LC-MS target-directed isolation yielded a series of new compounds, cymopolyphenols A−F (1–6), and two known phenylspirodrimanes, F1839-I (7) and stachybotrylactone (8). This is the first report of natural products from the recently described genus, Cymostachys. Compounds 1–6 and 8 contain a dihydroisobenzofuran moiety, and 4–6 are low-order polymers of 1 with novel scaffolds. The structures of the compounds were established by spectroscopic and spectrometric data interpretation, with further support from X-ray crystallography studies of 3 and 4. Compound 3 undergoes facile racemization in solution and was found to crystalize as a racemic mixture. Compound 5 was also obtained in racemic form, and after chiral chromatography, both separated enantiomers racemized in solution by a presumed keto-enol tautomerization. Compounds 1 and 3–6 were found to be weakly antimicrobial (MIC 16–64 μg/ml) in vitro against several Gram-positive and Gram-negative human or aquatic pathogens, compound 5 was shown to chelate iron in vitro at 10 μM, and 8 activated plant disease resistance in vivo in a transgenic model organism.