From Discovery to Production: Biotechnology of Marine Fungi for the Production of New Antibiotics

Abstract

Filamentous fungi are well known for their capability of producing antibiotic natural products. Recent studies have demonstrated the potential of antimicrobials with vast chemodiversity from marine fungi. Development of such natural products into lead compounds requires sustainable supply. Marine biotechnology can significantly contribute to the production of new antibiotics at various levels of the process chain including discovery, production, downstream processing, and lead development. However, the number of biotechnological processes described for large-scale production from marine fungi is far from the sum of the newly-discovered natural antibiotics. Methods and technologies applied in marine fungal biotechnology largely derive from analogous terrestrial processes and rarely reflect the specific demands of the marine fungi. The current developments in metabolic engineering and marine microbiology are not yet transferred into processes, but offer numerous options for improvement of production processes and establishment of new process chains. This review summarises the current state in biotechnological production of marine fungal antibiotics and points out the enormous potential of biotechnology in all stages of the discovery-to-development pipeline. At the same time, the literature survey reveals that more biotechnology transfer and method developments are needed for a sustainable and innovative production of marine fungal antibiotics.

Untitled

“…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 . Thus, marine-derived endophytic fungi prolong to be a potential source of unique secondary metabolites with interesting structural features, a significant number of which exhibited promising biological activities 22,23 . The disc diffusion method is extensively used to explore the preliminary anti-microbial activity of natural substances and plant extracts.…”

“…Some investigators also claimed that marine-derived Fusarium sp. 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 .…”

Antimicrobial discovery from natural and unusual sources

“…[39] Aureobasidium species release indanonaftol A, which is a spiro-indanone derivative, the first antibiotic compound isolated from marine yeast with reported antibacterial activities against Grampositive bacteria. [40,41] Ascochital, an aldehyde compound isolated from the marine ascomycete Kirschsteiniothelia maritima, possesses antibacterial activity against B. subtilis. [34] Pestalone is a chlorinated benzophenone antibiotic compound, isolated from the combined cultivation of the marine fungi of Pestalotia species (isolated from the surface of the Bahamian brown alga Rosenvingea species) and showed antibacterial activities against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus faecium.…”

“…Gram-positive bacteria Specific target site not determined [40,41] Streptomyces lincolnensis Lincomycin Gram-positive bacteria Inhibits protein synthesis [56] 8…”

Marine fungi in the spotlight: opportunities and challenges for marine fungal natural product discovery and biotechnology

“…Over 100 new fungal metabolites with various biological activities have been reported from phylogenetically diverse marine fungi. Marine fungal natural products lend themselves to large-scale biotechnological cultivation, presenting excellent opportunities in many areas, such as pharmaceuticals or cosmetics, or in food processing and agriculture [5]. Cephalosporin C, a second-line antibiotic was obtained from a Cephalosporium (now Acremonium ) sp.…”