Background: Terrein, a major secondary metabolite from Aspergillus terreus, shows great potentials in biomedical and agricultural applications. However, the low fermentation yield of terrein in wild A. terreus strains limits its industrial applications. Results: Here, we constructed a cell factory based on the marine-derived A. terreus RA2905, allowing for overproducing terrein by using starch as the sole carbon source. Firstly, the pathway-specific transcription factor TerR was over-expressed under the control of a constitutive gpdA promoter of A. nidulans, resulting in 5 to 16 folds up-regulation in terR transcripts compared to WT. As expected, the titer of terrein was improved in the two tested terR OE mutants when compared to WT. Secondly, the global regulator gene stuA, which was demonstrated to suppress the terrein synthesis in our analysis, was deleted, leading to greatly enhanced production of terrein. In addition, LS-MS/MS analysis showed that deletion of StuA cause decreased synthesis of the major byproduct butyrolactones. To achieve an optimal strain, we further refactored the genetic circuit by combining deletion of stuA and overexpression of terR, a higher terrein yield was achieved with a lower background of byproducts in double mutants. In addition, it was also found that loss of StuA (both ΔstuA and ΔstuA::OEterR) resulted in aconidial morphologies, but a slightly faster growth rate than that of WT. Conclusion: Our results demonstrated that refactoring both global and pathway-specific transcription factors (StuA and TerR) provides a high-efficient strategy to enhance terrein production, which could be adopted for large-scale production of terrein or other secondary metabolites in marine-derived filamentous fungi.

This study explores the impact of gut microbiota on body metabolites and the growth rate of sea cucumber seedlings. A comprehensive analysis using metabolomics and microbiomics was conducted to ascertain the gut microbiota and body metabolites in sea cucumber seedlings exhibiting varying growth rates. Distinct changes in the intestinal flora were observed in correlation with different growth rates of sea cucumber seedlings. The microbial communities of faster-growing seedlings exhibited greater diversity and evenness of taxa. For example, the abundance of genera Rhodococcus, Woeseia, Lysobacter, Desulfuromonadia_Sva1033, and Flavobacteriaceae_NS5_marine_group was more than 24 times higher in the fast-growing group compared to the slow-growing group. Metabolomics analysis revealed an association between high growth rates of cucumber seedlings and discrepancies in metabolites, such as amino acids, lipids, and carbohydrates. Isorenieratene, possibly synthesized by Rhodococcus, was more than 2.5 times more abundant in the fast-growing group than the slow-growing group. Slow-growing seedlings showed considerable enrichment of environmental pollutants, such as antibiotics and drugs, while their colonies were devoid of bacteria capable of degrading such pollutants. In addition, significant differences were observed between groups in the biosynthesis of amino acids, metabolism of arginine and proline, biosynthesis of unsaturated fatty acids, and metabolism of linoleic acid. Moreover, significant correlations between the microbial genera and sea cucumber metabolites were identified through correlation analysis. Significant differences exist in the gut microbiota and metabolite composition among seedlings with varying growth rates. Microbes residing in the gut have the potential to influence the growth of seedlings through modulation of their metabolism.

Background: Chemotherapy-induced premature ovarian failure represents a major challenge to female reproductive health, yet the potential regulatory role of vaginal microbiota in this process remains largely unexplored. Results: Using a well-established model of chemotherapy-induced ovarian aging, we observed significant disruptions in vaginal microbial ecology characterized by depletion of Lactobacillus species and concomitant enrichment of pathogenic bacteria. Microbiota transplantation effectively reversed these dysbiosis patterns and restored ovarian function. Single-cell transcriptomic analysis revealed that microbial intervention promoted the recovery of granulosa and luteal cell populations while simultaneously suppressing inflammatory activation in ovarian stromal cells, demonstrating the vaginal microbiota's capacity to maintain follicular integrity. Further mechanistic insights showed that microbiota transplantation upregulated key antioxidant defense systems and ribosomal protein networks within ovarian cells, suggesting coordinated actions to mitigate oxidative stress and enhance cellular repair capacity, although the specific microbial metabolites mediating these effects require further elucidation. Conclusions: Our findings establish for the first time the existence of a functional vaginal microbiota-ovary axis and delineate its critical role in protecting against chemotherapy-induced ovarian damage. This work not only advances our fundamental understanding of microbial-endocrine crosstalk but also identifies concrete microbial targets for developing innovative strategies to preserve fertility in cancer patients.