Hormaomycins B and C: New Antibiotic Cyclic Depsipeptides from a Marine Mudflat-Derived Streptomyces sp.

Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces sp., collected in Mohang, Korea. The planar structures of the hormaomycins, which bear structurally-unique units, such as 4-(Z)-propenylproline, 3-(2-nitrocyclopropyl)alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and β-methylphenylalanine, were established as the first natural analogues belonging to the hormaomycin peptide class. The absolute configurations of 1 and 2 were deduced by comparing their CD spectra with that of hormaomycin. These hormaomycins exhibited significant inhibitory effects against various pathogenic Gram-positive and Gram-negative bacteria.     

Secondary Metabolites from Marine-Derived Fungi and Actinobacteria as Potential Sources of Novel Colorectal Cancer Drugs

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality of life of people who are older, who are the most vulnerable subpopulation. This review presents recent updates regarding secondary metabolites derived from marine fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines HCT116, HT29, HCT15, RKO, Caco-2, and SW480. The observed marine-derived fungi were from the species Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp., and Westerdykella sp. Additionally, Streptomyces sp. and Nocardiopsis sp. are actinobacteria discussed in this study. Seventy one compounds reviewed in this study were grouped on the basis of their chemical structures. Indole alkaloids and diketopiperazines made up most compounds with higher potencies when compared with other groups. The potency of indole alkaloids and diketopiperazines was most probably due to halogen-based functional groups and sulfide groups, respectively.     

Secondary Metabolites from Marine-Derived Bacillus: A Comprehensive Review of Origins,Structures, and Bioactivities

The marine is a highly complex ecosystem including various microorganisms. Bacillus species is a predominant microbialflora widely distributed in marine ecosystems. This review aims to provide a systematic summary of the newly reported metabolites produced by marine-derived Bacillus species over recent years covering the literature from 2014 to 2021. It describes the structural diversity and biological activities of the reported compounds. Herein, a total of 87 newly reported metabolites are included in this article, among which 49 compounds originated from marine sediments, indicating that marine sediments are majority sources of productive strains of Bacillus species Therefore, marine-derived Bacillus species are a potentially promising source for the discovery of new metabolites.     

Structures and Biological Activities of Secondary Metabolites from Trichoderma harzianum

The biocontrol fungus Trichoderma harzianum, from both marine and terrestrial environments, has attracted considerable attention. T. harzianum has a tremendous potential to produce a variety of bioactive secondary metabolites (SMs), which are an important source of new herbicides and antibiotics. This review prioritizes the SMs of T. harzianum from 1988 to June 2022, and their relevant biological activities. Marine-derived SMs, especially terpenoids, polyketides, and macrolides compounds, occupy a significant proportion of natural products from T. harzianum, deserving more of our attention.     

Secondary Metabolites Isolated from Chilean Marine Algae: A Review

Chile is in the extreme southwestern part of America, and it has an extreme length, of approximately 4300 km that increases to 8000 km considering the Chilean Antarctic Territory. Despite the large extent of its coastal territory and the diversity of geographic environments and climates associated with Chilean coasts, the research on marine resources in Chile has been rather scarce. From marine organisms found in Chilean coastal waters, algae have been the most studied, since they contain a wide range of interesting secondary metabolites that have some structural traits that make them unique and uncharacteristic. Thus, a wide structural variety of natural products including terpenoids (monoterpenes, sesquiterpenes, diterpenes, and meroterpenoids), furanones, and C₁₅-acetogenins have been isolated and identified. This review describes the existing literature on bioprospecting and exploration of secondary metabolites from Chilean coasts.     

Isolation and Characterization of Anti-Adenoviral Secondary Metabolites from Marine Actinobacteria

Adenovirus infections in immunocompromised patients are associated with high mortality rates. Currently, there are no effective anti-adenoviral therapies available. It is well known that actinobacteria can produce secondary metabolites that are attractive in drug discovery due to their structural diversity and their evolved interaction with biomolecules. Here, we have established an extract library derived from actinobacteria isolated from Vestfjorden, Norway, and performed a screening campaign to discover anti-adenoviral compounds. One extract with anti-adenoviral activity was found to contain a diastereomeric 1:1 mixture of the butenolide secondary alcohols 1a and 1b. By further cultivation and analysis, we could isolate 1a and 1b in different diastereomeric ratio. In addition, three more anti-adenoviral butenolides 2, 3 and 4 with differences in their side-chains were isolated. In this study, the anti-adenoviral activity of these compounds was characterized and substantial differences in the cytotoxic potential between the butenolide analogs were observed. The most potent butenolide analog 3 displayed an EC₅₀ value of 91 μM and no prominent cytotoxicity at 2 mM. Furthermore, we propose a biosynthetic pathway for these compounds based on their relative time of appearance and structure.     

Secondary Metabolites from Penicillium pinophilum SD-272, a Marine Sediment-Derived Fungus

Two new secondary metabolites, namely, pinodiketopiperazine A (1) and 6,7-dihydroxy-3-methoxy-3-methylphthalide (2), along with alternariol 2,4-dimethyl ether (3) and l-5-oxoproline methyl ester (4), which were isolated from a natural source for the first time but have been previously synthesized, were characterized from the marine sediment-derived fungus Penicillium pinophilum SD-272. In addition, six known metabolites (5–10) were also identified. Their structures were elucidated by analysis of the NMR and mass spectroscopic data. The absolute configuration of compound 1 was determined by experimental and calculated ECD spectra. Compound 2 displayed potent brine shrimp (Artemia salina) lethality with LD₅₀ 11.2 μM.     

Discovery of New Secondary Metabolites from Marine Bacteria Hahella Based on an Omics Strategy

Hahella is one characteristic genus under the Hahellaceae family and shows a good potential for synthesizing new natural products. In this study, we examined the distribution of the secondary metabolite biosynthetic gene cluster (SMBGC) under Hahella with anti-SMASH. The results derived from five genomes released 70 SMBGCs. On average, each strain contains 12 gene clusters, and the most abundant ones (45.7%) are from the family of non-ribosomal peptide synthetase (NRPS) and non-ribosomal peptide synthetase hybrid with polyketide synthase (NRPS/PKS), indicating a great potential to find bioactive compounds. The comparison of SMBGC between H. chejuensis and other species showed that H. chejuensis contained two times more gene clusters than H. ganghwensis. One strain, designed as NBU794, was isolated from the mangrove soil of Dongzhai Port in Haikou (China) by iChip. The 16S rRNA gene of NBU794 exhibited 99% identity to H. chejuensis KCTC 2396 and clustered with the H. chejuensis clade on the phylogenetic trees. Genome mining on strain NBU794 released 17 SMBGCs and two groups of bioactive compounds, which are chejuenolide A-C and nine prodiginines derivatives. The prodiginines derivatives include the well-known lead compound prodigiosin and two new compounds, 2-methyl-3-pentyl-4-O-methyl-prodiginine and 2-methyl-3-octyl-prodiginine, which were identified through fragmentation analysis based on LC-MS/MS. The anti-microbial activity assay showed prodigiosin and 2-methyl-3-heptyl-prodiginine exhibited the best performance in inhibiting Escherichia coli, Salmonella paratyphi B, MASA Staphylococcus aureus, Bacillus subtilis, and Candida albicans. Moreover, the yield of prodigiosin in H. chejuensis NBU794 was also evaluated, which could reach 1.40 g/L under the non-optimized condition and increase to 5.83 g/L in the modified ISP4 medium with macroporous adsorption beads added, indicating that NBU794 is a promising source of prodigiosin.