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.
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