AUTHOR=Wang Tingting , Zhou Jing , Zou Jiabin , Shi Yutong , Zhou Wenli , Shao Peng , Yu Tianze , Cui Wei , Li Xiaohui , Wu Xingxin , Ye Jing , Yan Xiaojun , Naman C. Benjamin , Lazaro J. Enrico H. , He Shan 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.638610

DOI=10.3389/fmicb.2021.638610

ISSN=1664-302X

ABSTRACT=<p>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 (&lt;30 m) and half from MCEs (30–150 m), facilitated prioritization for further study a <italic>Cymostachys</italic> fungus from a 103 m deep <italic>Aaptos</italic> sponge. LC-MS target-directed isolation yielded a series of new compounds, cymopolyphenols A−F (<bold>1</bold>–<bold>6</bold>), and two known phenylspirodrimanes, F1839-I (<bold>7</bold>) and stachybotrylactone (<bold>8</bold>). This is the first report of natural products from the recently described genus, <italic>Cymostachys</italic>. Compounds <bold>1</bold>–<bold>6</bold> and <bold>8</bold> contain a dihydroisobenzofuran moiety, and <bold>4</bold>–<bold>6</bold> are low-order polymers of <bold>1</bold> 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 <bold>3</bold> and <bold>4</bold>. Compound <bold>3</bold> undergoes facile racemization in solution and was found to crystalize as a racemic mixture. Compound <bold>5</bold> was also obtained in racemic form, and after chiral chromatography, both separated enantiomers racemized in solution by a presumed keto-enol tautomerization. Compounds <bold>1</bold> and <bold>3</bold>–<bold>6</bold> were found to be weakly antimicrobial (MIC 16–64 μg/ml) <italic>in vitro</italic> against several Gram-positive and Gram-negative human or aquatic pathogens, compound <bold>5</bold> was shown to chelate iron <italic>in vitro</italic> at 10 μM, and <bold>8</bold> activated plant disease resistance <italic>in vivo</italic> in a transgenic model organism.</p>