Bioactive natural products from marine sponges and fungal endophytes

Abstract

This review highlights recent findings of our group on bioactive marine natural products isolated from marine sponges and marine derived fungi. The activated chemical defence of the Mediterranean sponge Aplysina aerophoba is introduced as an example of a dynamic response of marine sponges to wounding. Following tissue disrupture preformed brominated isoxazoline alkaloids are enzymatically cleaved and thereby give rise to aeroplysinin-1 which is believed to protect sponges from invasion of pathogenic bacteria. A preliminary characterization of the membrane bound enzyme(s) involved in the cleavage reaction is presented. Bromotyrosine derived, oxime group bearing peptides, the so called bastadins, obtained from the sponge Ianthella basta and some of their synthetic derivatives were shown to exhibit pronounced antifouling activity against larvae of the barnacle Balanus improvisus. The antifouling activity could be traced to the oxime group as an important pharmacophore that was also found to be present in other sponge derived natural products exhibiting antifouling activity. Marine derived fungi that reside within invertebrates such as sponges or inside Mangrove plants are emerging as a new source of bioactive metabolites as demonstrated for Aspergillus ustus and Alternaria sp. that were isolated from the sponge Suberites domuncula or from the Mangrove plant Sonneratia alba, respectively. The former fungus yielded new moderately cytotoxic sesquiterpenoids of the drimane type whereas the latter was found to produce polyketides such as alternariol that exhibited strong and selective inhibitory activity against several protein kinases, for instance Aurora A and B which are targets for anticancer chemotherapy.

Publication impact in sponge chemical and microbial ecology

“…Some sponges may produce their own biologically active natural products against predators, competitors, or foulers, and others may benefit from the defensive properties of the metabolites produced by their microbes (Pawlik et al 1995, Newbold et al 1999, Amsler et al 2000. Though chemical defences have been well studied in the phylum Porifera (Müller et al 2004, Sipkema et al 2005, Proksch et al 2010, and it has been the preferred phylum of the marine natural product community over the last 50 years (Blunt et al 2015), the origin of many compounds still remains controversial (König et al 2006, Wang 2006, Hentschel et al 2012.…”

“…Our goal is to help identify the audience and impact of these research lines, which can result in improved research questions, better journal selection and increased repercussion of these topics. Some book chapters and reviews published in the literature in the last four to five years exhaustively compile and analyse papers in both sponge ecology areas: chemistry (Proksch et al 2010, Paul et al 2011, Genta-Jouve and Thomas 2012 and microbiology (Hentschel et al 2012, Schippers et al 2012, Thacker and Freeman 2012. Consequently, rather than a traditional, narrative review of the literature, we took a quantitative approach based on a series of bibliometric indicators that offer an unbiased analysis of both sponge disciplines and highlight themes that will demand additional research in the near future.…”

Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.

“…The resulting homogenate was diluted with sterile seawater at three dilutions (1:10, 1:100, and 1:1 000). For fungi cultivation, small pieces of sponge tissue or 100 µL of each dilution was plated onto the three agar plates of the following media: potato dextrose agar (PDA) medium ( [3][4] weeks until the morphology of fungi could be distinguished. Pure cultures were used for morphological identification by light microscopy.…”

“…Microbial natural products are an important source and play a significant role in the discovery and understanding of cellular pathways that are essential in the drug discovery process. In the search for new bioactive natural products from marine organisms, increasing attention is being given to microorganisms such as bacteria and fungi [3][4][5] . Particularly sponge-derived fungal cultures…”

Induced production of depsipeptides by co-culturing Fusarium tricinctum and Fusarium begoniae

“…[1][2][3][4] However, finding new and promising microbial natural products is becoming increasingly difficult as the rate of rediscovery is getting gradually higher. Several strategies have been reported to trigger biosynthetic pathways which remain silent under standard laboratory culture conditions.…”