Hybrid Polyketides from a Hydractinia-Associated Cladosporium sphaerospermum SW67 and Their Putative Biosynthetic Origin.

Seoung Rak Lee,Ki Sung Kang,Dahae Lee,Yoon-Joo Ko,Chung Sub Kim,Maja Rischer,Christine Beemelmanns,Ki Hyun Kim,Hee Jeong Eom

doi:10.3390/md17110606

Abstract

Five hybrid polyketides (1a, 1b, and 2–4) containing tetramic acid core including a new hybrid polyketide, cladosin L (1), were isolated from the marine fungus Cladosporium sphaerospermum SW67, which was isolated from the marine hydroid polyp of Hydractinia echinata. The hybrid polyketides were isolated as a pair of interconverting geometric isomers. The structure of 1 was determined based on 1D and 2D NMR spectroscopic and HR-ESIMS analyses. Its absolute configuration was established by quantum chemical electronic circular dichroism (ECD) calculations and modified Mosher’s method. Tetramic acid-containing compounds are reported to be derived from a hybrid PKS-NRPS, which was also proved by analyzing our 13C-labeling data. We investigated whether compounds 1–4 could prevent cell damage induced by cisplatin, a platinum-based anticancer drug, in LLC-PK1 cells. Co-treatment with 2 and 3 ameliorated the damage of LLC-PK1 cells induced by 25 μM of cisplatin. In particular, the effect of compound 2 at 100 μM (cell viability, 90.68 ± 0.81%) was similar to the recovered cell viability of 88.23 ± 0.25% with 500 μM N-acetylcysteine (NAC), a positive control.

Highlights

Marine invertebrates host a diverse assemblage of mostly beneficial microbes that play important roles in host development, fitness, and protection [1,2]
C. sphaerospermum SW67 was cultivated on a large scale on potato dextroseasagar (PDA) and MEA agar plates for 14
C. sphaerospermum SW67 was cultivated on a large scale on PDA and MEA agar plates for 14 days days ◦at 25 °C

Summary

Introduction

Marine invertebrates host a diverse assemblage of mostly beneficial microbes that play important roles in host development, fitness, and protection [1,2]. To ensure propagation within these often extreme and highly competitive host-specific microenvironments, microorganisms have developed unique metabolic and physiological capabilities that aid in their survival [3,4]. Amongst many other important biochemical traits, marine microorganisms are well known to produce structurally diverse and unique secondary metabolites, which often show important pharmacological activities, such as antioxidant, antibiotic, anticancer, or anti-inflammatory activities [5,6,7,8,9]. Previous reports have shown interesting marine natural products, e.g., hypochromins A and B were isolated from Hypocrea vinisa; penicillinolide. Mar. Drugs 2019, 17, x were isolated from Hypocrea vinisa; penicillinolide A, a 10-membered lactone, was purified 2from

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Results

Conclusion