A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

Abstract

A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated.

Heterologous Expression of Ilicicolin H Biosynthetic Gene Cluster and Production of a New Potent Antifungal Reagent, Ilicicolin J

“…1 H and 13 C-NMR spectroscopic data of Ilicicolin J (400 and 100 MHz, DMSO- d 6 ) and Ilicicolin H (400 and 100 MHz, DMSO- d 6 ); Table S5. NMR chemical shifts of Ilicicolin H in DMSO- d 6 and reported [34] Ilicicolin H in Acetonitrile- d 3 ; Figure S8. The 1 H-NMR (400 MHz, DMSO- d 6 ) and 13 C-NMR (100 MHz, DMSO- d 6 ) spectrum of the Ilicicolin J; Figure S9.…”

Metabolomics and Marine Biotechnology: Coupling Metabolite Profiling and Organism Biology for the Discovery of New Compounds

“…Bioassay-guided fractionation (i.e., extract fractionation and purification based on targeted activities) has been classically used for the discovery of new natural products (Kildgaard et al, 2017;El Menif et al, 2019). However, this approach is not only time-consuming, but often results in the isolation of previously known compounds, since molecule dereplication is performed at the end of the workflow (Herath et al, 2019;Pereira et al, 2019).…”

Dereplication by High-Performance Liquid Chromatography (HPLC) with Quadrupole-Time-of-Flight Mass Spectroscopy (qTOF-MS) and Antiviral Activities of Phlorotannins from Ecklonia cava

“…Dereplication is the term that is used to discover new natural materials through the rapid identification of compounds that are based on new analytical tools, such as MS and NMR spectroscopy, to avoid the re-isolation of known components. In particular, the rapid development of modern MS techniques has accelerated dereplication strategies using high-performance liquid chromatography—quadrupole time-of-flight mass (HPLC-qTOFMS) spectra with tandem database searching to identify the known compounds in the extract [21]. By increasing the use of high-resolution mass spectrometry (HRMS) for measuring exact masses, the concept of “mass defect” is also increasingly being used in natural products research [22].…”