Streptomyces species are attractive sources of secondary metabolites that serve as major sources of antibiotics and other drugs. In this study, genome mining was used to determine the biosynthetic potential of Streptomyces sp. 21So2-11 isolated from Antarctic soil. 16S rRNA gene sequencing revealed that this strain is most closely related to Streptomyces drozdowiczii NBRC 101007T, with a similarity of 98.02%. Genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) showed that strain 21So2-11 represents a novel species of the genus Streptomyces. In addition to a large number of genes related to environmental adaptation and ecological function, a total of 28 putative biosynthetic gene clusters (BGCs) responsible for the biosynthesis of known and/or novel secondary metabolites, including terpenes, lantipeptides, polyketides, nonribosomal peptides, RiPPs and siderophores, were detected in the genome of strain 21So2-11. In addition, a total of 1456 BGCs were predicted to contribute to the biosynthesis of more than 300 secondary metabolites based on the genomes of 47 Streptomyces strains originating from polar regions. The results indicate the potential of Streptomyces sp. 21So2-11 for bioactive secondary metabolite production and are helpful for understanding bacterial adaptability and ecological function in cold terrestrial environments.

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2-7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1-7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

Fusarium pseudograminearum causes destructive crown disease in wheat. The velvet protein family is a crucial regulator in development, virulence, and secondary metabolism of fungi. We conducted a functional analysis of FpVelB using a gene replacement strategy. The deletion of FpVelB decreased radial growth and enhanced conidial production compared to that of wild type. Furthermore, FpVelB modulates the fungal responses to abiotic stress through diverse mechanisms. Significantly, virulence decreased after the deletion of FpVelB in both the stem base and head of wheat. Genome-wide gene expression profiling revealed that the regulation of genes by FpVelB is associated with several processes related to the aforementioned phenotype, including \"immune\", \"membrane\", and \"antioxidant activity\", particularly with regard to secondary metabolites. Most importantly, we demonstrated that FpVelB regulates pathogen virulence by influencing deoxynivalenol production and modulating the expression of the PKS11 gene. In conclusion, FpVelB is crucial for plant growth, asexual development, and abiotic stress response and is essential for full virulence via secondary metabolism in F. pseudograminearum.

Sclareol, a diterpene alcohol, is the most common starting material for the synthesis of ambrox, which serves as a sustainable substitute for ambergris, a valuable fragrance secreted by sperm whales. Sclareol has also been proposed to possess antibacterial, antifungal, and anticancer activities. However, in nature, sclareol is only produced by a few plant species, including Cistus creticus, Cleome spinosa, Nicotiana glutinosa, and Salvia sclarea, which limits its commercial application. In this study, we cloned the two genes responsible for sclareol biosynthesis in S. sclarea, labda-13-en-8-ol diphosphate synthase (LPPS) and sclareol synthase (SS), and overexpressed them in tobacco (Nicotiana tabacum L.). The best transgenic tobacco lines accumulated 4.1 μg/cm2 of sclareol, which is comparable to the sclareol production of N. glutinosa, a natural sclareol producer. Thus, sclareol synthesis in tobacco represents a potential alternative means for the production of this high-value compound.

Guanine nucleotide-binding proteins of the ADP ribosylation factor (Arf) family and their activating proteins (Arf-GAPs) are essential for diverse biological processes. Here, two homologous Arf-GAPs, Age1 (AoAge1) and Age2 (AoAge2), were identified in the widespread nematode-trapping fungus Arthrobotrys oligospora. Our results demonstrated that AoAge1, especially AoAge2, played crucial roles in mycelial growth, sporulation, trap production, stress response, mitochondrial activity, DNA damage, endocytosis, reactive oxygen species production, and autophagy. Notably, transcriptome data revealed that approximately 62.7% of the genes were directly or indirectly regulated by AoAge2, and dysregulated genes in Aoage2 deletion were enriched in metabolism, ribosome biogenesis, secondary metabolite biosynthesis, and autophagy. Furthermore, Aoage2 inactivation caused a substantial reduction in several compounds compared to the wild-type strain. Based on these results, a regulatory network for AoAge1 and AoAge2 was proposed and verified using a yeast two-hybrid assay. Based on our findings, AoAge1 and AoAge2 are essential for vegetative growth and mycelial development. Specifically, AoAge2 is required for sporulation and trapping morphogenesis. Our results demonstrated the critical functions of AoAge1 and AoAge2 in mycelial growth, diverse cellular processes, and pathogenicity, offering deep insights into the functions and regulatory mechanisms of Arf-GAPs in nematode-trapping fungi.

Trichoderma spp. can enhance plant resistance against a wide range of biotic stressors. However, the fundamental mechanisms by which Trichoderma enhances plant resistance against Meloidogyne incognita, known as root-knot nematodes (RKNs), are still unclear. Here, we identified a strain of Trichoderma asperellum (T141) that could effectively suppress RKN infestation in tomato (Solanum lycopersicum L.). Nematode infestation led to an increase in the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) in roots but pre-inoculation with T141 significantly decreased oxidative stress. The reduction in ROS and MDA was accompanied by an increase in the activity of antioxidant enzymes and the accumulation of flavonoids and phenols. Moreover, split root test-based analysis showed that T141 inoculation in local roots before RKN inoculation increased the concentration of phytohormone jasmonate (JA) and the transcripts of JA synthesis and signaling-related genes in distant roots. UPLC-MS/MS-based metabolomics analysis identified 1051 differentially accumulated metabolites (DAMs) across 4 pairwise comparisons in root division test, including 81 flavonoids. Notably, 180 DAMs were found in comparison between RKN and T141-RKN, whereas KEGG annotation and enrichment analysis showed that the secondary metabolic pathways, especially the flavonoid biosynthesis, played a key role in the T141-induced systemic resistance to RKNs. The role of up-regulated flavonoids in RKN mortality was further verified by in vitro experiments with the exogenous treatment of kaempferol, hesperidin and rutin on J2-stage RKNs. Our results revealed a critical mechanism by which T141 induced resistance of tomato plants against the RKNs by systemically promoting secondary metabolism in distant roots.

Actinomycetes, a diverse group of bacteria with filamentous growth characteristics, have long captivated researchers and biochemists for their prolific production of secondary metabolites. Among the myriad roles played by actinomycete secondary metabolites, their historical significance in the field of biocontrol stands out prominently. The fascinating journey begins with the discovery of antibiotics, where renowned compounds like streptomycin, tetracycline, and erythromycin revolutionized medicine and agriculture. The history of biocontrol traces its roots back to the early twentieth century, when scientists recognized the potential of naturally occurring agents to combat pests and diseases. The emergence of synthetic pesticides in the mid-twentieth century temporarily overshadowed interest in biocontrol. However, with growing environmental concerns and the realization of the negative ecological impacts of chemical pesticides, the pendulum swung back towards exploring sustainable alternatives. Beyond their historical role as antibiotics, actinomycete-produced secondary metabolites encompass a rich repertoire with biopesticide potential. The classification of these compounds based on chemical structure and mode of action is highlighted, demonstrating their versatility against both plant pathogens and insect pests. Additionally, this review provides in-depth insights into how endophytic actinomycete strains play a pivotal role in biocontrol strategies. Case studies elucidate their effectiveness in inhibiting Spodoptera spp. and nematodes through the production of bioactive compounds. By unraveling the multifunctional roles of endophytic actinomycetes, this review contributes compelling narrative knowledge to the field of sustainable agriculture, emphasizing the potential of these microbial allies in crafting effective, environmentally friendly biocontrol strategies for combating agricultural pests.

Heavy metal copper (Cu) will inevitably impact the marine macroalgae Gracilariopsis lemaneiformis (G. lemaneiformis), which is a culture of economic importance along China\'s coastline. In this study, the detoxification mechanism of Cu stress on G. lemaneiformis was revealed by assessing physiological indicators in conjunction with transcriptome and metabolome analyses at 1 d after Cu stress. Our findings revealed that 25 μM Cu stimulated ROS synthesis and led to the enzymatic oxidation of arachidonic acid residues. This process subsequently impeded G. lemaneiformis growth by suppressing photosynthesis, nitrogen metabolism, protein synthesis, etc. The entry of Cu ions into the algae was facilitated by ZIPs and IRT transporters, presenting as Cu2+. Furthermore, there was an up-regulation of Cu efflux transporters HMA5 and ABC family transporters to achieve compartmentation to mitigate the toxicity. The results revealed that G. lemaneiformis elevated the antioxidant enzyme superoxide dismutase and ascorbate-glutathione cycle to maintain ROS homeostasis. Additionally, metabolites such as flavonoids, 3-O-methylgallic acid, 3-hydroxy-4-keto-gama-carotene, and eicosapentaenoic acid were up-regulated compared with the control, indicating that they might play roles in response to Cu stress. In summary, this study offers a comprehensive insight into the detoxification mechanisms driving the responses of G. lemaneiformis to Cu exposure.

This study addresses the increasing concern regarding cyanotoxin contamination of water bodies, highlighting the diversity of these toxins and their potential health implications. Cyanobacteria, which are prevalent in aquatic environments, produce toxic metabolites, raising concerns regarding human exposure and associated health risks, including a potential increase in cancer risk. Although existing research has primarily focused on well-known cyanotoxins, recent technological advancements have revealed numerous unknown cyanotoxins, necessitating a comprehensive assessment of multiple toxin categories. To enhance the cyanotoxin databases, we optimized the CyanoMetDB cyanobacterial secondary metabolites database by incorporating secondary fragmentation patterns using the Mass Frontier fragmentation data prediction software. Water samples from diverse locations in Shanghai were analyzed using high-resolution mass spectrometry. Subsequently, the toxicity of cyanobacterial metabolites in the water samples was examined through acute toxicity assays using the crustacean Thamnocephalus platyurus. After 24 h of exposure, the semi-lethal concentrations (LC50) of the water samples ranged from 0.31 mg L-1 to 1.78 mg L-1 (MC-LR equivalent concentration). Our findings revealed a critical correlation between the overall concentration of cyanobacterial metabolites and toxicity. The robust framework and insights of this study underscore the need for an inclusive approach to water quality management, emphasizing continuous efforts to refine detection methods and comprehend the broader ecological impact of cyanobacterial blooms on aquatic ecosystems.

Prevalent neurological disorders such as Alzheimer\'s disease, Parkinson\'s disease, and stroke are increasingly becoming a global burden as society ages. It is well-known that degeneration and loss of neurons are the fundamental underlying processes, but there are still no effective therapies for these neurological diseases. In recent years, plenty of studies have focused on the pharmacology and feasibility of natural products as new strategies for the development of drugs that target neurological disorders. Antrodia camphorata has become one of the most promising candidates, and the crude extracts and some active metabolites of it have been reported to play various pharmacological activities to alleviate neurological symptoms at cellular and molecular levels. This review highlights the current evidence of Antrodia camphorata against neurological disorders, including safety evaluation, metabolism, blood-brain barrier penetration, neuroprotective activities, and the potential on regulating the gut-microbiome-brain axis. Furthermore, potential strategies to resolve problematic issues identified in previous studies are also discussed. We aim to provide an overview for the ongoing development and utilization of Antrodia camphorata in cerebral neuropathology.