Kyuho Moon

Chemical analysis of the marine-derived Saccharopolyspora sp. PG10 led to the isolation of a novel macrolactam, cebulactam A₃ (1), along with four known congeners, cebulactams A₁ and A₂ (2 and 3) and shengliangmycins B and D (4 and 5). The structure of 1 was established by high-resolution mass spectrometry (HRMS) and comprehensive nuclear magnetic resonance (NMR) analyses, and its absolute configuration was determined using Mosher’s method. Genome analysis identified a putative biosynthetic gene cluster consistent with a hybrid polyketide pathway. Antimicrobial evaluation revealed that shengliangmycin B exhibited the strongest activity, whereas cebulactam analogs exhibited weaker effects. These findings expand the structural diversity of cebulactam-type macrolactams and provide insights into their stereochemical variation.

Nine new brominated macrolactam glycosides, daklakamitocins A–I (1–9), were isolated from bromide-supplemented cultures of Amycolatopsis sp. CK6, a strain isolated from a red soil sample collected in Dak Lak Province, Vietnam. Their structures were elucidated using NMR spectroscopy, high-resolution mass spectrometry (HRMS), and electronic circular dichroism (ECD) spectroscopy. Daklakamitocin A (1) exhibited markedly stronger cytotoxicity against human cancer cell lines than its chlorinated analogue, ansacarbamitocin A, suggesting that bromination may contribute to enhanced antiproliferative activity. These findings expand the chemical diversity of maytansinoid metabolites and highlight halide supplementation as an effective strategy for generating brominated congeners for structure–activity comparison.

Genome-guided mining of marine Streptomyces sp. GCU-142 led to the identification of three unprecedented sugar-bearing anthracycline glycosides, igidamycins A-C (1-3). The structures of 1-3 were assigned by spectroscopic analysis including NMR, HR-MS, and UV spectroscopy. Their configurations were determined by ROESY NMR data, the modified Mosher's method, l-cysteine methyl ester derivatization, and TD-DFT ECD calculations. Bioinformatic analysis suggested a plausible biosynthetic pathway of igidamycins, integrating type II polyketide assembly, extensive sugar tailoring, and late-stage nitration. Notably, igidamycin A (1), bearing a nitro group at C-6, exhibited potent antibacterial activity against various Gram-positive pathogens. In contrast, the non-nitrated congeners (2 and 3) were inactive, highlighting a key role of the nitro functionality in its antibacterial potency.

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides distinguished by their lasso-like, threaded topology. Common to all lasso peptides biosynthetic gene clusters examined so far is an arrangement whereby the precursor peptide is encoded adjacent to the macrolactam synthetase and other modification genes. Here we report the cebulassopins A-D (1-4), the first example of lasso peptides synthesized by a split operon whereby multiple precursors are encoded several Mbps distant from the modification enzymes. Aside from characterizing their structures and calculating the three-dimensional topology of 1 and 2, we also find that the cebulassopins are potent antiproliferative agents with sub-μM inhibitory concentrations against human lung carcinoma cells. These results set the stage for further biological examination and exploration of other split lasso peptide gene clusters.

Streptomyces sp. AWH31-250, isolated from a tidal mudflat in the Nakdong River estuary in Busan, Republic of Korea, was found to produce two novel p-aminoacetophenone derivatives, mohangic acid H (1) and mohangiol (2). Their planar structures were established by comprehensive 1D and 2D NMR spectroscopy, mass spectrometry, and UV analysis, possessing a shorter carbon-chain with a diene moiety, whereas known mohangic acids A–F bear a longer carbon-chain with a triene moiety. The absolute configurations of the key stereogenic centers were determined via computational DP4+ calculations and bioinformatic analysis of the ketoreductase domain sequence from the biosynthetic gene cluster. Based on the careful gene analysis along with whole-genome sequencing, the first plausible biosynthetic pathway of mohangic acids A–G and mohangiol was proposed. Mohangic acid H (1) and mohangiol (2) displayed moderate inhibitory activity against Candida albicans isocitrate lyase with IC₅₀ values of 21.37 and 21.12 µg/mL, respectively.

Opportunistic fungal pathogens, responsible for over 300 million severe cases and 1.5 million deaths annually, pose a serious global health threat, especially in immunocompromised individuals. Among these, Candida albicans is a major cause of both superficial and invasive infections, which can progress to systemic candidiasis. One of the critical factors in C. albicans pathogenicity is the yeast-to-hyphal transition, which enables biofilm formation and promotes tissue invasion through the secretion of candidalysin, a cytolytic peptide toxin encoded by the ECE1 gene. In this study, metabolites produced by Streptomyces ambofaciens CJD34, isolated from soil samples, were screened for antifungal activity. Methoxy-apo-enterobactin (compound 1) was identified as a potential inhibitor of C. albicans virulence. Treatment with compound 1 significantly suppressed ECE1 expression and candidalysin production. In a murine subcutaneous infection model, topical application of compound 1 reduced subcutaneous colonization by C. albicans. Molecular docking analysis suggested that the inhibition of ECE1 expression was not mediated by direct binding to known upstream transcription factors, indicating an indirect mechanism of action. Collectively, these findings highlight compound 1 as a promising antivirulence agent targeting candidalysin-mediated pathogenicity in C. albicans.

A mild and biocompatible strategy for the site-selective alkylation of quinoxalinones via photoinduced dehydrogenative alkylation has been developed. This protocol enables the functionalization of both unprotected quinoxalinone and nonreactive dihydroquinoxalinone under DNA-compatible conditions. The optimized reaction proceeds efficiently while tolerating a diverse range of alkyl donors from various radical precursors. Given its simplicity and DNA compatibility, this methodology offers a platform for the construction of DNA-encoded libraries incorporating a privileged quinoxalinone scaffold.

Covering: 1992 to 2024 Type-I polyketide synthase (PKS)-derived metabolites are structurally diverse bioactive natural products containing multiple stereogenic centres. This review focuses on the configurational analysis of type-I PKS-derived natural products, emphasizing the methodologies and challenges associated with determining their stereochemistry due to their complex structures with multiple chiral centres. Key strategies include J-based configuration analysis (JBCA), chemical derivatizations with chiral reagents, degradation methods, NMR spectroscopic analysis, and the exploitation of chiroptical properties. Case studies demonstrate the practical applications of these methods in elucidating the stereochemistry of type-I polyketide natural products.

Rho-associated protein kinase (ROCK) inhibitors are promising therapeutic agents for reducing elevated intraocular pressure in patients with glaucoma. We explored new ROCK inhibitors derived from bioactive metabolites produced by microbes, specifically cryptic metabolites from Nocardiopsis sp. MCY7, using a liquid chromatography-mass spectrometry-based chemical analysis approach integrated with metal stress-driven isolation. This strategy led to the identification of two previously undescribed linear peptides, nocarnickelamides A and B (1 and 2), and an unreported cittilin derivative, cittilin C (3). The planar structures of 1-3 were elucidated using UV spectroscopy, high-resolution mass spectrometry, and nuclear magnetic resonance. The absolute configurations of 1 and 2 were assigned using the advanced Marfey's method. Biological assays demonstrated that nocarnickelamides (1 and 2) exhibited dual inhibitory activity against ROCK1 (IC₅₀ 29.8 and 14.9 μM, respectively) and ROCK2 (IC₅₀ 27.0 and 21.9 μM, respectively), with molecular simulations suggesting binding to the ATP-binding site. In human trabecular meshwork cells, 2 significantly inhibited the activation of ROCK-regulated cytoskeletal contraction markers such as the myosin light chain. Nocarnickelamide B (2) is a novel dual ROCK1/2 inhibitor and a potential pharmacophore for designing new therapeutic agents to reduce intraocular pressure in glaucoma.

In this study, metagenomic analysis was employed to investigate the bacterial communities in the Muan tidal mudflat of the Republic of Korea. We used metagenomic analysis to identify the microbial community in tidal soil dominated by Proteobacteria. From this environment, the bacterial strain, Saccharomonospora sp. CMS18, was isolated and yielded two previously unknown compounds, penipaline D (3) and N-acetyl-dimethylallyltryptophan (4). The chemical structures of the isolated compounds along with 6-dimethylallyl-indole (1), 6-dimethylallyltryptophan (2), penipaline D (3), and N-acetyl-dimethylallyltryptophan (4) were structurally investigated using HR-ESI-MS and NMR spectroscopy. The isolated compound 6-dimethylallyl-indole (1) demonstrated broad-spectrum antifungal activity, with IC₅₀ value of 0.04 mM against Candida glabrata and 0.35 mM against both Candida albicans and Cryptococcus neoformans. Additionally, it exhibited additive interaction with caspofungin against C. albicans.