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Staphylococcus aureus , a common foodborne pathogen, has a close association with agriculture and food. With the rapid emergence and widespread dissemination of antimicrobial resistance, efforts have been directed toward developing and studying new antimicrobial compounds to inhibit the growth of S. aureus and other foodborne pathogens, thereby preventing contamination and ensuring food safety. Herein, we reported eight new aromatic polyketides, naphpyrones A-H ( 1 - 8 ), from the heterologous expression strain Streptomyces coelicolor A3(2)/ spi1 Δ spi H3. Their structures and absolute configurations were elucidated by extensive NMR, MS, theoretical NMR calculations, DP4+ probability analysis, Mosher's method, and ECD analyses. Notably, naphpyrone A ( 1 ) featured an unprecedented 6/6/6/6/5 neocyclic skeleton. Bioactivity evaluation revealed that compounds 1 and 2 exhibited antibacterial activity against S. aureus , with MIC values of 1 μg/mL and 4 μg/mL, respectively. These findings highlight the potential for screening and developing therapeutic agents from actinomycetes -derived aromatic polyketides against food pathogens.

Six new angucycline structures, including spirocyclione A ( 1 ), which contains an unusual oxaspiro[5.5]undecane architecture, and its ring-A-cleaved product spirocyclione B ( 2 ), were discovered by heterologous expression of a type II polyketide biosynthetic gene cluster captured from a marine actinomycete strain Streptomyces sp. HDN155000. Three flavoprotein monooxygenases are confirmed to be responsible for the oxidative carbon skeleton rearrangements in the biosynthesis of compounds 1 and 2 . The obtained compounds showed promising cytotoxicity against different types of cancer cells.

Prenyltransferases play important roles in the diversification of natural products and the improvement of biological activities. A UbiA-type prenyltransferase CdnC with substrate promiscuity was identified as the pivotal builder of the noncanonical chrodrimanin skeletons, which carry a benzo-cyclohexanone structure as the nonterpene part. In vitro and heterologous expression studies with CdnC led to the production of a series of novel chrodrimanin-like structures. The discovery of CdnC offers a referable strategy for the biosynthesis and structural diversification of farnesyl-derived meroterpenoids.

A new indole alkaloid, named taichunamide H (1), was obtained from cultures of the fungus Aspergillus versicolor. With observation of a carbon resonance with a chemical shift of 190.4 ppm, generally thought to be a carbonyl, the structure of 1 was initially proposed to be a diastereomer of taichunamide A that contains a unique spiro-azetidine moiety. Further analysis of compound 1 using X-ray diffraction showed that the spiro-azetidine moiety should be revised as a fused-imine-containing pyrrole ring, with the resonance at 190.4 ppm assigned as an imine carbon. Accordingly, the structure of taichunamide A was also revised.

Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure-function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure-function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (∼300 nm) with moderate charge densities (<10 mV). This convergence in polymer structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.

Bactofection offers a gene delivery option particularly useful in the context of immune modulation. The bacterial host naturally attracts recognition and cellular uptake by antigen presenting cells (APCs) as the initial step in triggering an immune response. Moreover, depending on the bacterial vector, molecular biology tools are available to influence and/or overcome additional steps and barriers to effective antigen presentation. In this work, molecular engineering was applied using Escherichia coli as a bactofection vector. In particular, the bacteriophage ΦX174 lysis E (LyE) gene was designed for variable expression across strains containing different levels of lysteriolysin O (LLO). The objective was to generate a bacterial vector with improved attenuation and delivery characteristics. The resulting strains exhibited enhanced gene and protein release and inducible cellular death. In addition, the new vectors demonstrated improved gene delivery and cytotoxicity profiles to RAW264.7 macrophage APCs.

Seven new prenylated indole diketopiperazines, versicamides A-G (1-7) and a novel chemical derivative from 7, versicamide H (8), along with three known analogic diketopiperazines (9-11) were obtained from the marine-derived fungus Aspergillus versicolor HDN08-60. Their structures were determined by spectroscopic techniques, including 2D NMR, ECD calculations, and single-crystal X-ray diffraction analysis, together with the assistance of further chemical conversions. The cytotoxicities of 1-8 were tested against the HeLa, HCT-116, HL-60, and K562 cell lines, but only 8 exhibited moderate activity against HL-60 cells, with an IC50 value of 8.7 μM. Further investigation with target screening showed that 8 exhibited selective PTK inhibitory activities.