Cihunamides A–D (1–4), novel antibacterial RiPPs, were isolated from volcanic‐island‐derived Streptomyces sp. The structures of 1–4 were elucidated by 1H, 13C, and 15N NMR, MS, and chemical derivatization; they contain a tetrapeptide core composed of WNIW, cyclized by a unique C−N linkage between two Trp units. Genome mining of the producer strain revealed two biosynthetic genes encoding a cytochrome P450 enzyme and a precursor peptide. Heterologous co‐expression of the core genes demonstrated the biosynthesis of cihunamides through P450‐mediated oxidative Trp‐Trp cross‐linking. Further bioinformatic analysis uncovered 252 homologous gene clusters, including that of tryptorubins, which possess a distinct Trp‐Trp linkage. Cihunamides do not display the non‐canonical atropisomerism shown in tryptorubins, which are the founding members of the “atropitide” family. Therefore, we propose to use a new RiPP family name, “bitryptides”, for cihunamides, tryptorubins, and their congeners, wherein the Trp‐Trp linkages define the structural class rather than non‐canonical atropisomerism.

A marine-derived actinomycete (Streptomyces sp. MBTI36) exhibiting antibacterial activities was investigated in the present study. The strain was identified using genetic techniques. The 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces microflavus. Furthermore, a new chromomycin A9 (1), along with chromomycin Ap (2), chromomycin A2 (3), and chromomycin A3 (4), were isolated from the ethyl acetate extract. Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, and HRMS, as well as comparisons with previously reported data. Compounds 1–4 showed potent antibacterial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). During a passage experiment, minimum inhibitory concentration (MIC) values for compounds 1–4 showed no more than a 4-fold increase from the starting MIC value, indicating that no resistance was detected over the 21 passages.

Four new peptides were isolated from the culture broths of the marine-derived fungi Aspergillus allahabadii and A. ochraceopetaliformis. Based on the results of chemical and spectroscopic analyses, two compounds (1 and 2) from A. allahabadii were determined to be cyclopentapeptides, while those from A. ochraceopetaliformis were a structurally-related cyclodepsihexapeptide (3) and its linear analog (4). In addition to the presence of a D-amino acid residue, the almost reversed sequence of peptides in 3 and 4, relative to those of the 1 and 2, is notable. These new compounds exhibited moderate inhibition against the enzyme sortase A as well as a weak inhibition against isocitrate lyase (2).

Thirteen coumarins (1–13), including five new compounds (1–5), were isolated from the folk medicinal plant Poncirus trifoliata. Combined spectroscopic analyses revealed that coumarins 1–4 are bis-isoprenylated coumarins with diverse oxidation patterns, while 5 is an enantiomeric di-isoprenylated coumarin. The absolute configurations of the stereogenic centers in the isoprenyl chains were assigned through MTPA and MPA methods, and those of the known compounds triphasiol (6) and ponciol (7) were also assigned using similar methods. These coumarins inhibited significantly Staphylococcus aureus-derived sortase A (SrtA), a transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall in Gram-positive bacteria. The present results obtained indicated that the bioactivity and underlying mechanism of action of these coumarins are associated with the inhibition of SrtA-mediated S. aureus adhesion to eukaryotic cell matrix proteins including fibrinogen and fibronectin, thus potentially serving as SrtA inhibitors.

Seven alkaloidal compounds (2–8) and one polyketide (1) were isolated from a semisolid rice culture of the marine-derived fungus Aspergillus sp. F452. Structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported data. The alkaloidal compounds (2–8) displayed weak to moderate inhibitory activities against Staphylococcus aureus-derived sortase A (SrtA) without affecting cell viability. Aspermytin A (1) strongly inhibited SrtA activity, with an IC50 value of 146.0 μM, and significantly reduced bacterial adherence to fibronectin-coated surfaces. The present results indicate that the underlying mechanism of action of compound 1 is associated with the inhibition of SrtA-mediated S. aureus adhesion to fibronectin, thus potentially serving as an SrtA inhibitor.