Resistance of pathogenic microorganisms against antimicrobials is a major threat to contemporary human society. It necessitates a perpetual influx of novel antimicrobial compounds. More specifically, Gram− pathogens emerged as the most exigent danger. In our continuing quest to search for novel antimicrobial molecules, alkaloids from marine fungi show great promise. However, current reports of such newly discovered alkaloids are often limited to cytotoxicity studies and, moreover, neglect to discuss the enigma of their biosynthesis. Yet, the latter is often a prerequisite to make them available through sufficiently efficient processes. This review aims to summarize novel alkaloids with promising antimicrobial properties discovered in the past five years and produced by marine fungi. Several discovery strategies are summarized, and knowledge gaps in biochemical production routes are identified. Finally, links between the structure of the newly discovered molecules and their activity are proposed. Since 2015, a total of 35 new antimicrobial alkaloids from marine fungi were identified, of which 22 showed an antibacterial activity against Gram− microorganisms. Eight of them can be classified as narrow-spectrum Gram− antibiotics. Despite this promising ratio of novel alkaloids active against Gram− microorganisms, the number of newly discovered antimicrobial alkaloids is low, due to the narrow spectrum of discovery protocols that are used and the fact that antimicrobial properties of newly discovered alkaloids are barely characterized. Alternatives are proposed in this review. In conclusion, this review summarizes novel findings on antimicrobial alkaloids from marine fungi, shows their potential as promising therapeutic candidates, and hints on how to further improve this potential.
The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria.
15 November 2018 in Biotechnology and Bioengineering
The field of astrobiology aims to understand the origin of life on Earth and searches for evidence of life beyond our planet. Although there is agreement on some of the requirements for life on Earth, the exact process by which life emerged from prebiotic conditions is still uncertain, leading to various theories. In order to expand our knowledge of life and our place in the universe, scientists look for signs of life through the use of biosignatures, observations that suggest the presence of past or present life. These biosignatures often require up-close investigation by orbiters and landers, which have been employed in various space missions. Mars, because of its proximity and Earth-like environment, has received the most attention and has been explored using (sub)surface sampling and analysis. Despite its inhospitable surface conditions, Venus has also been the subject of space missions due to the presence of potentially habitable conditions in its atmosphere. In addition, the discovery of habitable environments on icy moons has sparked interest in further study. This article provides an overview of the origin of life on Earth and the astrobiology studies carried out by orbiters and landers.
30 August 2024 in Applied Microbiology and Biotechnology
Streptomyces species are experts in the production of bioactive secondary metabolites; however, their taxonomy has fallen victim of the tremendous interest
The performance of a microbial fermentation on an industrial scale is subjected to the robustness of the strain. Such strains are genetically engineered to optimize the production of desired compounds in minimal time, but they often fail to maintain high productivity levels for many generations, hindering their effective application in industrial conditions. This study focused on assessing the impact of genomic instability in yeasts that were engineered to produce a fluorescent output by incorporating a reporter gene at one or more genomic locations. The fermentation performance of these strains was evaluated over 100 generations in a sequential batch set-up. In order to bridge the gap between strain engineering and industrial implementation, we proposed the use of novel, host-specific parameters to standardize the strain robustness and evaluate potential improvements. It was observed that yeasts carrying multiple copies of the reporter gene exhibited a more pronounced decrease in output, and the genomic integration site significantly influenced the production. By leveraging these new, host-specific parameters, it becomes possible to anticipate strain behavior prior to incurring substantial costs associated with large-scale production. This approach enhances the economic viability of novel microbial fermentation processes and narrows the divide between laboratory findings and industrial applications.