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.

Bioactive compounds were detected in crude extracts of the fungus, Calcarisporium sp. KF525, which was isolated from German Wadden Sea water samples. Purification of the metabolites from the extracts yielded the five known polyesters, 15G256α, α-2, β, β-2 and π (1–5), and five new derivatives thereof, named calcarides A–E (6–10). The chemical structures of the isolated compounds were elucidated on the basis of one- and two-dimensional NMR spectroscopy supported by UV and HRESIMS data. The compounds exhibited inhibitory activities against Staphylococcus epidermidis, Xanthomonas campestris and Propionibacterium acnes. As the antibacterial activities were highly specific with regard to compound and test strain, a tight structure-activity relationship is assumed.

As part of an international research project, the marine fungal strain collection of the Helmholtz Centre for Ocean Research (GEOMAR) research centre was analysed for secondary metabolite profiles associated with anticancer activity. Strain MF458 was identified as Tolypocladium geodes, by internal transcribed spacer region (ITS) sequence similarity and its natural product production profile. By using five different media in two conditions and two time points, we were able to identify eight natural products produced by MF458. As well as cyclosporin A (1), efrapeptin D (2), pyridoxatin (3), terricolin A (4), malettinins B and E (5 and 6), and tolypocladenols A1/A2 (8), we identified a new secondary metabolite which we termed tolypocladenol C (7). All compounds were analysed for their anticancer potential using a selection of the NCI60 cancer cell line panel, with malettinins B and E (5 and 6) being the most promising candidates. In order to obtain sufficient quantities of these compounds to start preclinical development, their production was transferred from a static flask culture to a stirred tank reactor, and fermentation medium development resulted in a nearly eight-fold increase in compound production. The strain MF458 is therefore a producer of a number of interesting and new secondary metabolites and their production levels can be readily improved to achieve higher yields.

Salar de Huasco at the Chilean Altiplano of the Atacama Desert is considered a polyextreme environment, where solar radiation, salinity and aridity are extremely high and occur simultaneously. In this study, a total of 76 bacterial isolates were discovered from soil samples collected at two different sites in the east shoreline of Salar de Huasco, including H0 (base camp next to freshwater stream in the north part) and H6 (saline soils in the south part). All isolated bacteria were preliminarily identified using some of their phenotypic and genotypic data into the genera Streptomyces (86%), Nocardiopsis (9%), Micromonospora (3%), Bacillus (1%), and Pseudomonas (1%). Streptomyces was found dominantly in both sites (H0 = 19 isolates and H6 = 46 isolates), while the other genera were found only in site H0 (11 isolates). Based on the genotypic and phylogenetic analyses using the 16S rRNA gene sequences of all Streptomyces isolates, 18% (12 isolates) revealed <98.7% identity of the gene sequences compared to those in the publicly available databases and were determined as highly possibly novel species. Further studies suggested that many Streptomyces isolates possess the nonribosomal peptide synthetases-coding gene, and some of which could inhibit growth of at least two test microbes (i.e., Gram-positive and Gram-negative bacteria and fungi) and showed also the cytotoxicity against hepatocellular carcinoma and or mouse fibroblast cell lines. The antimicrobial activity and cytotoxicity of these Streptomyces isolates were highly dependent upon the nutrients used for their cultivation. Moreover, the HPLC-UV-MS profiles of metabolites produced by the selected Streptomyces isolates unveiled apparent differences when compared to the public database of existing natural products. With our findings, the polyextreme environments like Salar de Huasco are promising sources for exploring novel and valuable bacteria with pharmaceutical potentials.