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

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

doi:10.3389/fmicb.2021.638610

Abstract

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.

Highlights

Natural products research has long been instrumental in generating lead molecules for drug discovery, and many natural products have reached the clinic without structural modification by medicinal chemistry (Cragg et al, 2009; Lachance et al, 2012; Agarwal et al, 2020; Newman and Cragg, 2020)
More natural product studies have been reported on mesophotic zone organisms after being collected by a remotely operated vehicle (ROV) or autonomous underwater vehicle (AUV)
The fungal strains were divided into two groups of each n = 40, representing shallow reef and Mesophotic coral ecosystems (MCEs) origins of the sponges that yielded the isolated microbial samples

Summary

Introduction

Natural products research has long been instrumental in generating lead molecules for drug discovery, and many natural products have reached the clinic without structural modification by medicinal chemistry (Cragg et al, 2009; Lachance et al, 2012; Agarwal et al, 2020; Newman and Cragg, 2020). Studies of marine organisms were at one point considered to be pioneering, and thousands of marine natural products have been reported These have provided a resource for drug development and, “as shown at the global marine pharmaceutical pipeline website, there are currently nine approved marinederived pharmaceuticals, and an additional 31 compounds are either in Phase I, II, and III of clinical pharmaceutical development” (Mayer et al, 2020). More natural product studies have been reported on mesophotic zone organisms after being collected by a remotely operated vehicle (ROV) or autonomous underwater vehicle (AUV). This practice is very costly and usually reserved for studying the much deeper bathypelagic and abyssopelagic zones, or even hadopelagic trenches (Schupp et al, 2009). Technical scientific diving is more eco-friendly than dredging and more cost-effective and efficient than using an ROV or AUV for sample collection

Methods

Results

Conclusion