The Neglected Marine Fungi, Sensu stricto, and Their Isolation for Natural Products’ Discovery

Abstract

Despite the rapid development of molecular techniques relevant for natural product research, culture isolates remain the primary source from which natural products chemists discover and obtain new molecules from microbial sources. Techniques for obtaining and identifying microbial isolates (such as filamentous fungi) are thus of crucial importance for a successful natural products’ discovery program. This review is presented as a “best-practices guide” to the collection and isolation of marine fungi for natural products research. Many of these practices are proven techniques used by mycologists for the isolation of a broad diversity of fungi, while others, such as the construction of marine baiting stations and the collection and processing of sea foam using dilution to extinction plating techniques, are methodological adaptations for specialized use in marine/aquatic environments. To this day, marine fungi, Sensu stricto, remain one of the few underexplored resources of natural products. Cultivability is one of the main limitations hindering the discovery of natural products from marine fungi. Through encouraged collaboration with marine mycologists and the sharing of historically proven mycological practices for the isolation of marine fungi, our goal is to provide natural products chemists with the necessary tools to explore this resource in-depth and discover new and potentially novel natural products.

Untitled

“…The importance of fungi as a new source of bioactive compounds was first focused by the discovery of penicillin from Penicillium notatum in 1928 by Alexander Flemming. A molecular study reported that fungal communities differ between marine lives collected at the same site and also differ from those present in the surrounding marine water [18][19][20] . Up to 2016, nearly 600 new compounds were reported from marinederived symbiotic microorganisms of which over 70% were obtained from epi/endophytes derived from marine weeds, invertebrates and woody substrates 21 .…”

“…is able to produce novel anti-bacterial compounds like cyclodepsipeptide enniatin B37, sesterterpenoid neomangicols 22,37 , bromomethylchlamydosporols A38 and antifungal compound, fusarielin E37. So, it can be assumed that the investigated marine fungi can produce antimicrobial secondary metabolites like pest alone due to bacterial competition against other micro-organisms in the marine environment developed through its chemical defense mechanisms 20 . Thus, the five isolates derived from four marine weeds are presumed to be good antibiotic-producer candidates.…”

Marine Microbial Diversity as a Source of Bioactive Natural Products

“…The challenging question of the isolation of marine fungi sensu stricto is key to the future exploration of the chemical diversity of marine fungi, and possibly the exploitation of their secondary metabolites. A best-practice guide for the isolation of marine fungi from different matrixes and their conservation is presented by Overy et al [11]. Generalist, osmotolerant/halotolerant genera such as Aspergillus and Penicillium are highly cited in the literature but taxonomic groups composed predominantly of marine fungi sensu stricto such as Halosphaeriaceae, Torpedosporales, and Lulworthiales have been little studied for now.…”

“…The fungus Geosmithia pallida FS140 was isolated from a sediment collected at 2403 m depth in the South China Sea [14]. Twelve diketopiperazines, including the three new thiodiketopiperazines geospallins A-C (6-8), were isolated from this fungus (Figure 1 In the sea, many fungal species are associated with macroscopic organisms [9,11,15]. The isolation of marine fungi from macroorganisms' tissues may in fact be a fairly straightforward way of isolating marine fungi sensu stricto.…”

“…Four new isocoumarin derivatives, namely botryospyrones A, B (10), C, and D ( Figure 2) were isolated from this fungus. Interestingly, a fifth compound (11) was produced only when the culture medium was supplemented with the host plant flavonoid (2R,3R)-3,5,7-trihydroxyflavanone 3-acetate, which had been found to slightly inhibit the endophyte growth. Owing to the ease of isomerization of animals by successive ring-opening and ring-closing steps, it is expected that such compound would eventually generate the more stable stereoisomer, i.e., the cis ring junction isomer.…”