Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC.

Four new cyclic pentapeptides, avellanins D–G (1–4), together with four known compounds (5–8), were isolated from a mangrove-derived Aspergillus fumigatus GXIMD 03099 fungus from Acanthus ilicifolius L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey’s method. Compounds 1–8 were screened for insecticidal and antibacterial activities. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with an LC₅₀ value of 86.6 µM; compound 4 had weak activity against Vibrio harveyi with an MIC value of 5.85 µM.

Background: Macrolactins, a type of macrolide antibiotic, are toxic to the producer strains. As such, its level is usually maintained below the lethal concentration during the fermentation process. To improve the production of macrolactins, we applied adaptive laboratory evolution technology to engineer a saline-resistant mutant strain. The hypothesis that strains with saline resistance show improved macrolactins production was investigated. Results: Using saline stress as a selective pressure, we engineered a mutant strain with saline resistance coupled with enhanced macrolactins production within 60 days using a self-made device. As compared with the parental strain, the evolved strain produced macrolactins with 11.93% improvement in non-saline stress fermentation medium containing 50 g/L glucose, when the glucose concentration increased to 70 g/L, the evolved strain produced macrolactins with 71.04% improvement. RNA sequencing and metabolomics results revealed that amino acid metabolism was involved in the production of macrolactins in the evolved strain. Furthermore, genome sequencing of the evolved strain revealed a candidate mutation, hisD^D41Y, that was causal for the improved MLNs production, it was 3.42 times higher than the control in the overexpression hisD^D41Y strain. Results revealed that saline resistance protected the producer strain from feedback inhibition of end-product (macrolide antibiotic), resulting in enhanced MLNs production. Conclusions: In the present work, we successfully engineered a mutant strain with enhanced macrolactins production by adaptive laboratory evolution using saline stress as a selective pressure. Based on physiological, transcriptomic and genetic analysis, amino acid metabolism was found to benefit macrolactins production improvement. Our strategy might be applicable to improve the production of other kinds of macrolide antibiotics and other toxic compounds. The identification of the hisD mutation will allow for the deduction of metabolic engineering strategies in future research.

Five previously undescribed peptaibiotics, including one 7-mer lipopeptaibol named lipotrichaibol A (1), and four 11-mer peptaibiotics named trichoderpeptides A-D (2–5) were isolated from the rice culture medium of the sponge-derived fungus Trichoderma sp. GXIMD 01001. Their structures and absolute configurations were unambiguously established by extensive spectroscopic data analysis and advanced Marfey’s method. All isolated compounds were evaluated via CCK8 bioassays to investigate their antiproliferative activity. Only compound 1 exerted potent cytotoxicity against HT-29 and DLD-1 cells with IC₅₀ values at 10.3 ± 1.9 and 12.31 ± 1.5 μM, respectively. In further in vitro bioassay, compound 1 exhibited significant inhibition in colony formation assay, induced apoptosis and blocked the cell cycle in the G0/G1 phase. The mechanism may be related to the regulation of the Erk1/2 signaling pathway.

Mangrove endophytic fungi are recognized as prolific sources of structurally diverse and bioactive natural products. In this study, 19 cultivable endophytic fungal strains were isolated and taxonomically characterized from mangrove plant tissues collected at the Shankou Mangrove Nature Reserve (Guangxi, China). One isolate, Aspergillus sclerotiorum BM19, exhibited broad-spectrum inhibitory activity against multiple aquatic pathogenic Vibrio strains. Bioactivity-guided fractionation of its ethyl acetate crude extract led to the isolation of penicillic acid (1), whose structure was fully elucidated by 1D/2D NMR and HRESIMS. Penicillic acid showed potent anti Vibrio parahaemolyticus activity with a minimum inhibitory concentration (MIC) of 6.25 μg/mL and displayed no obvious cytotoxicity toward human HaCaT keratinocytes. Growth curve assays revealed a concentration-dependent antibacterial effect: 0.5 × MIC delayed logarithmic growth, whereas 1 × and 2 × MIC completely suppressed bacterial proliferation. Transmission electron microscopy (TEM) visualized cellular distortion, compromised cell envelopes, and cytoplasmic leakage at MIC, with severe envelope disruption at 2 × MIC. Confocal laser scanning microscopy (CLSM) combined with SYTO 9/PI double staining further confirmed the concentration-dependent impairment of cell envelope integrity, as evidenced by reduced green fluorescence (intact cells) and increased red fluorescence (damaged cells). Collectively, these findings indicate that penicillic acid inhibits V. parahaemolyticus and is associated with concentration-dependent impairment of cell-envelope integrity. Although penicillic acid is a known mycotoxin, its selective activity against pathogenic vibrios and low toxicity to human keratinocytes highlight its potential as a lead compound for aquaculture applications. Nevertheless, further systematic evaluation of in vivo efficacy and biosafety is required prior to translational development.