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The genus Actinokineospora (family Pseudonocardiaceae) has recently emerged as a prolific source of structurally diverse, biologically active specialized metabolites. Actinokineospora spp. are filamentous actinomycetes isolated from various terrestrial biotopes. The genus is still sparsely represented taxonomically, with only 19 species holding validly published names and genome sequences available for an additional six strains. Nevertheless, Actinokineospora appears to have one of the highest biosynthetic novelty index values among actinomycetes, making it a prime candidate for the discovery of new specialized metabolites. To date, several Actinokineospora strains have shown antimicrobial activity, including Actinokineospora acnipugnans R434^T, Actinokineospora alba 03-9939^T, Actinokineospora fastidiosa NRRL B-16697^T, Actinokineospora riparia C-39162^T, Actinokineospora sp. G85, and Actinokineospora sp. PR83; the active compounds from these strains remain to be identified and characterized. By contrast, detailed chemical characterization has been achieved for several producers: Actinokineospora spheciospongiae EG49^T (polyketides actinospene and actinosporins; the lasso peptide actinokineosin), Actinokineospora bangkokensis 44EHW^T (polyene thailandins), Actinokineospora fastidiosa ATCC 202099 (nocathiacin thiopeptides), Actinokineospora sp. UTMC 2448 (persiathiacin thiopeptides), and Actinokineospora auranticolor DSM 44650^T (kineomіcin glycopeptides). Collectively, these findings establish Actinokineospora as a promising yet underexplored genus for antibiotic discovery and biosynthetic engineering. In this review, we summarize current knowledge on Actinokineospora spp. and provide an in-depth account of specialized metabolite production for those compounds whose structures have been elucidated. Full article

Lemonomycin (1) was first isolated from the fermentation broth of Streptomyces candidus in 1964. The complete chemical structure was not elucidated until 2000 with extensive spectroscopic analysis. Lemonomycin is currently known as the only glycosylated tetrahydroisoquinoline antibiotic. Its potent antibacterial activity against Staphylococcus aureus and Bacillus subtilis and complex architecture make it an ideal target for total synthesis. In this short review, we summarize the research status of lemonomycin for biological activity, biosynthesis, and chemical synthesis. The unique deoxy aminosugar-lemonose was proposed to play a crucial role in biological activity, as shown in other antibiotics, such as arimetamycin A, nocathiacin I, glycothiohexide α, and thiazamycins. Given the self-resistance of the original bacterial host, the integration of biosynthesis and chemical synthesis to pursue efficient synthesis and further derivatization is in high demand for the development of novel antibiotics to combat antibiotic-resistant infections. Full article

Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources. Full article