Phage therapy: A renewed approach against oral diseases caused by Enterococcus faecalis infections.

Antibiotics play an important role in the treatment of infectious diseases. Long-term overuse or misuse of antibiotics, however, has triggered the global crisis of antibiotic resistance, bringing challenges to treating clinical infection. Bacteriophages (phages) are the viruses infecting bacterial cells. Due to high host specificity, high bactericidal activity, and good biosafety, phages have been used as natural alternative antibacterial agents to fight against multiple drug-resistant bacteria. Enterococcus faecalis is the main species detected in secondary persistent infection caused by failure of root canal therapy. Due to strong tolerance and the formation of biofilm, E. faecalis can survive the changes in pH, temperature, and osmotic pressure in the mouth and thus is one of the main causes of periapical lesions. This paper summarizes the advantages of phage therapy, its applications in treating oral diseases caused by E. faecalis infections, and the challenges it faces. It offers a new perspective on phage therapy in oral diseases.

A novel holin from an Enterococcus faecalis phage and application in vitro and in vivo.

Enterococcus faecalis, a conditional pathogenic bacterium, is prevalent in the intestinal, oral, and reproductive tracts of humans and animals, causing a variety of infectious diseases. E. faecalis is the main species detected in secondary persistent infection from root canal therapy failure. Due to the abuse of antibacterial agents, E. faecalis has evolved its resistant ability. Therefore, it is difficult to treat clinical diseases infected by E. faecalis. Exploring new alternative drugs for treating E. faecalis infection is urgent. We cloned and expressed the gene of phage holin, purified the recombinant protein, and analyzed the antibacterial activity, lysis profile, and ability to remove bacterial biofilm. It showed that the crude enzyme of phage holin pEF191 exhibited superior bacterial inhibiting activity and a broader lysis host range compared to the parent phage PEf771. In addition, pEF191 demonstrated high efficacy in eliminating E. faecalis biofilm. The therapeutic results of the Sprague-Dawley (SD) rats model infected showed that pEf191 did not affect SD rats, indicating that pEF191 provided greater protection against E. faecalis infection in SD rats. Based on the 16 S rDNA data of SD rats intestinal microorganism population, holin pEF191 exhibited no impact on the diversity of intestinal microorganisms at the phylum and genus levels and improved the relative abundance of favorable bacteria. Thus, pEF191 may serve as a promising alternative to antibiotics in the management of E. faecalis infection.

NADH-dependent formate dehydrogenase mutants for efficient carbon dioxide fixation.

Bioconversion of CO2 to high-valuable products is a globally pursued sustainable technology for carbon neutrality. However, low CO2 activation with formate dehydrogenase (FDH) remains a major challenge for further upcycling due to the poor CO2 affinity, reduction activity and stability of currently used FDHs. Here, we present two recombined mutants, ΔFDHPa48 and ΔFDHPa4814, which exhibit high CO2 reduction activity and antioxidative activity. Compared to FDHPa, the reduction activity of ΔFDHPa48 was increased up to 743 % and the yield in the reduction of CO2 to methanol was increased by 3.16-fold. Molecular dynamics identified that increasing the width of the substrate pocket of ΔFDHPa48 could improve the enzyme reduction activity. Meanwhile, the enhanced rigidity of C-terminal residues effectively protected the active center. These results fundamentally advanced our understanding of the CO2 activation process and efficient FDH for enzymatic CO2 activation and conversion.

Viral AMGs-driven pentose phosphate pathway in natural wetland.

Viruses exist anywhere on earth where there is life, and among them, virus-encoded auxiliary metabolic genes (AMGs) can maintain ecosystem balance and play a major role in the global ecosystem. Although the function of AMGs has been widely reported, the genetic diversity of AMGs in natural ecosystems is still poorly understood. Exploring the genetic diversity of viral community-wide AMGs is essential to gain insight into the complex interactions between viruses and hosts. In this article, we studied the phylogenetic tree, principal co-ordinates analysis (PCoA), α diversity, and metabolic pathways of viral auxiliary metabolism genes involved in the pentose phosphate pathway (PPP) through metagenomics, and the changes of metabolites and genes of host bacteria were further studied by using Pseudomonas mandelii SW-3 and its lytic phage based on metabolic flow and AMGs expression. We found that the viral AMGs in the Napahai plateau wetland were created by a combination of various external forces, which contributed to the rich genetic diversity, uniqueness, and differences of the virus, which promoted the reproduction of offspring and better adaptation to the environment. Overall, this study systematically describes the genetic diversity of AMGs associated with the PPP in plateau wetland ecosystems and further expands the understanding of phage-host unique interactions.

Whole genome analysis of Pseudomonas mandelii SW-3 and the insights into low-temperature adaptation.

Pseudomonas mandelii SW-3, isolated from the Napahai plateau wetland, can survive in cold environments. The mechanisms underlying the survival of bacteria in low temperatures and high altitudes are not yet fully understood. In this study, the whole genome of SW-3 was sequenced to identify the genomic features that may contribute to survival in cold environments. The results showed that the genome size of strain SW-3 was 6,538,059 bp with a GC content of 59%. A total of 67 tRNAs, a 34,110 bp prophage sequence, and a large number of metabolic genes were found. Based on 16S rRNA gene phylogeny and average nucleotide identity analysis among P. mandelii, SW-3 was identified as a strain belonging to P. mandelii. In addition, we clarified the mechanisms by which SW-3 survived in a cold environment, providing a basis for further investigation of host-phage interaction. P. mandelii SW-3 showed stress resistance mechanisms, including glycogen and trehalose metabolic pathways, and antisense transcriptional silencing. Furthermore, cold shock proteins and glucose 6-phosphate dehydrogenase may play pivotal roles in facilitating adaptation to cold environmental conditions. The genome-wide analysis provided us with a deeper understanding of the cold-adapted bacterium.

Diversity and composition of active and total bacteria in rhizospheric soil in response to continuous cropping years of Panax notoginseng.

The synchronous research and analysis of total and active soil microbial communities can provide insight into how these communities are impacted by continuous cropping years and pathogen infection. The diversity of total and active bacteria in rhizospheric soil of 2-year-old and 3-year-old healthy and diseased Panax notoginseng can comprehensively reveal the bacterial response characteristics in continuous cropping practice. The results showed that 4916 operational taxonomic units (OTUs) were found in the rhizospheric soil bacterial community of P. notoginseng at the DNA level, but only 2773 OTUs were found at the RNA level. The rhizospheric environment had significant effects on the active and bacterial communities, as indicated by the number of OTUs, Shannon, Chao1, Faith's phylogenetic diversity (Faith's PD), and Simpson's diversity indexes. The DNA level can better show the difference in diversity level before and after infection with root rot. The bacterial Chao1 and Faith's PD diversity indexes of 2-year-old root rot-diseased P. notoginseng rhizospheric soil (D2) were higher than that of healthy plants, while the bacterial Shannon diversity index of 3-year-old root rot-diseased P. notoginseng rhizospheric soil (D3) was the lowest in the total bacteria. Principal coordinate analysis (PCoA) illustrated that the total bacterial species composition changed markedly after root rot disease. There were significant differences in the composition of active bacterial species between the 2-year and 3-year rhizospheres. In conclusion, the total and active edaphic rhizospheric bacterial communities could provide important opportunities to understand the responses of bacteria to continuous cropping of P. notoginseng. Differential responses of total and active edaphic rhizosphere bacterial communities to continuous cropping of Panax notoginseng.

Diversity and function of viral AMGs associated with DNA biosynthesis in the Napahai plateau wetland.

Viruses play an important role in microbial community structure and biodiversity by lysing host cells, and can also affect host metabolic pathways by expressing auxiliary metabolic genes (AMGs). As a unique low-latitude, high-altitude seasonal plateau wetland in China, Napahai has high research value. However, studies on the genetic diversity of AMGs and viruses associated with DNA biosynthesis have not been reported. Based on metagenomics, with the phylogenetic tree, PCoA, and α diversity analysis, we found that three DNA biosynthesis-related viral AMGs (cobS, mazG, and purM) in the Napahai plateau wetland were rich in genetic diversity, uniqueness, and differences compared with other habitats and host sources. Through the KEGG metabolic pathway and metabolic flow analysis of Pseudomonas mandelii (SW-3) and phage (VSW-3), the AMGs (cobS, mazG, and purM) genes of the three related viruses involved in DNA biosynthesis were upregulated and their expression increased significantly. In general, we systematically described the genetic diversity of AMGs associated with DNA biosynthesis in plateau wetland ecosystems and clarified the contribution of viral AMGs in the Napahai plateau wetland to DNA biosynthesis, as well as the changes of metabolites and genes. It further expands the understanding of phage-host interactions, which is of great significance for further revealing the role of viral AMGs in the biological evolution and biogeochemical cycle of wetland ecosystems.

Revealing viral diversity in the Napahai plateau wetland based on metagenomics.

We focused on exploring the diversity of viruses in the Napahai plateau wetland, a unique ecosystem located in Yunnan, China. While viruses in marine environments have been extensively studied for their influence on microbial metabolism and biogeochemical cycles, little is known about their composition and function in plateau wetlands. Metagenomic analysis was employed to investigate the viral diversity and biogeochemical impacts in the Napahai wetland. It revealed that the Caudoviricetes and Malgrandaviricetes class level was the most abundant viral category based on phylogenetic analysis. Additionally, a gene-sharing network highlighted the presence of numerous unexplored viruses and demonstrated their unique characteristics and significant variation within the viral community of the Napahai wetland. Furthermore, the study identified the auxiliary metabolic genes (AMGs). AMGs provide phages with additional functions, such as protection against host degradation and involvement in metabolic pathways, such as the pentose phosphate pathway and DNA biosynthesis. The viruses in the Napahai wetland were found to influence carbon, nitrogen, sulfur, and amino acid metabolism, indirectly contributing to biogeochemical cycling through these AMGs. Overall, the research sheds light on the diverse and unique viral communities in the Napahai plateau wetland and emphasizes the significant roles of viruses in microbial ecology. The findings contribute to a deeper understanding of the characteristics and ecological functions of viral communities in plateau wetland ecosystems.

Comprehensive insights into the mechanism of keratin degradation and exploitation of keratinase to enhance the bioaccessibility of soybean protein.

Keratin is a recalcitrant protein and can be decomposed in nature. However, the mechanism of keratin degradation is still not well understood. In this study, Bacillus sp. 8A6 can completely degrade the feather in 20 h, which is an efficient keratin degrader reported so far. Comprehensive transcriptome analysis continuously tracks the metabolism of Bacillus sp. 8A6 throughout its growth in feather medium. It reveals for the first time how the strain can acquire nutrients and energy in an oligotrophic feather medium for proliferation in the early stage. Then, the degradation of the outer lipid layer of feather can expose the internal keratin structure for disulfide bonds reduction by sulfite from the newly identified sulfite metabolic pathway, disulfide reductases and iron uptake. The resulting weakened keratin has been further proposedly de-assembled by the S9 protease and hydrolyzed by synergistic effects of the endo, exo and oligo-proteases from S1, S8, M3, M14, M20, M24, M42, M84 and T3 families. Finally, bioaccessible peptides and amino acids are generated and transported for strain growth. The keratinase has been applied for soybean hydrolysis, which generates 2234 peptides and 559.93 mg/L17 amino acids. Therefore, the keratinases, inducing from the poultry waste, have great potential to be further applied for producing bioaccessible peptides and amino acids for feed industry.

Function and distribution of nitrogen-cycling microbial communities in the Napahai plateau wetland.

Nitrogen is an essential component of living organisms and a major nutrient that limits life on Earth. Until now, freely available nitrogen mainly comes from atmospheric nitrogen, but most organisms rely on bioavailable forms of nitrogen, which depends on the complex network of microorganisms with a wide variety of metabolic functions. Microbial-mediated nitrogen cycling contributes to the biogeochemical cycling of wetlands, but its specific microbial abundance, composition, and distribution need to be studied. Based on the metagenomic data, we described the composition and functional characteristics of microbial nitrogen cycle-related genes in the Napahai plateau wetland. Six nitrogen cycling pathways existed, such as dissimilatory nitrate reduction, denitrification, nitrogen fixation, nitrification, anammox, and nitrate assimilation. Most genes related to the nitrogen cycling in this region come from bacteria, mainly from Proteobacteria and Acidobacteria. Habitat types and nitrogen cycle-related genes largely explained the relative abundance of total nitrogen pathways. Phylogenetic trees were constructed based on nitrogen cycle-related genes from different habitats and sources, combined with PCoA analysis, most of them clustered separately, indicating richness and uniqueness. Some microbial groups seemed to be special or general in the nitrogen cycling. In conclusion, it suggested that microorganisms regulated the N cycling process, and may lead to N loss throughout the wetland, thus providing a basis for further elucidation of the microbial regulation of N cycling processes and the Earth's elemental cycles.

[Effect of viral infection on host cell metabolism: a review].

As specialized intracellular parasite, viruses have no ability to metabolize independently, so they completely depend on the metabolic mechanism of host cells. Viruses use the energy and precursors provided by the metabolic network of the host cells to drive their replication, assembly and release. Namely, viruses hijack the host cells metabolism to achieve their own replication and proliferation. In addition, viruses can also affect host cell metabolism by the expression of auxiliary metabolic genes (AMGs), affecting carbon, nitrogen, phosphorus, and sulfur cycles, and participate in microbial-driven biogeochemical cycling. This review summarizes the effect of viral infection on the host's core metabolic pathway from four aspects: cellular glucose metabolism, glutamine metabolism, fatty acid metabolism, and viral AMGs on host metabolism. It may facilitate in-depth understanding of virus-host interactions, and provide a theoretical basis for the treatment of viral diseases through metabolic intervention.

[Development of enzyme immobilization systems for CO2 bioconversion: advances and challenges].

Enzyme-catalyzed CO2 reduction to value-added commodities is important for alleviating the global environmental issues and energy crises due to high selectivity and mild conditions. Owing to high energy density, formic acid or methanol produced from CO2 using formate dehydrogenase (FDH) or multi-enzyme cascades are promising target chemicals for CO2 utilization. However, the low activity, poor stability and low reusability of key enzymes involved in such process hampered its large-scale application. Enzyme immobilization provides an effective solution to these problems and significant progress have been made in immobilization carriers. Moreover, integration of enzyme immobilization with other catalysis techniques have been explored extensively. This review summarized the recent advances in the immobilization of enzymes using membranes, inorganic materials, metal-organic frameworks, covalent organic frameworks and other carriers, and illustrated the characteristics and advantages of different immobilization materials and immobilization methods. The synergistic effects and applications of immobilized enzymes and electrocatalytic or photocatalytic coupling reaction systems for CO2 reduction were further summarized. Finally, the current challenges of enzyme immobilization technology and coupling reaction systems were pointed out and their development prospects were presented.

Whole genome analysis and cold adaptation strategies of Pseudomonas sivasensis W-6 isolated from the Napahai plateau wetland.

Microbial communities of wetlands play key roles in the earth's ecology and stability. To elucidate the cold adaptation mechanisms of bacteria in plateau wetlands, we conducted comparative genomic analyses of Pseudomonas sivasensis and closely related lineages. The genome of P. sivasensis W-6, a cold-adapted bacterium isolated from the Napahai plateau wetland, was sequenced and analyzed. The genome length was 6,109,123 bp with a G+C content of 59.5%. Gene prediction yielded 5360 protein-coding sequences, 70 tRNAs, 24 gene islands, and 2 CRISPR sequences. The isolate contained evidence of horizontal gene transfer events during its evolution. Two prophages were predicted and indicated that W-6 was a lysogen. The cold adaptation of the W-6 strain showed psychrophilic rather than psychrotrophic characteristics. Cold-adapted bacterium W-6 can utilize glycogen and trehalose as resources, associated with carbohydrate-active enzymes, and survive in a low-temperature environment. In addition, the cold-adapted mechanisms of the W-6 included membrane fluidity by changing the unsaturated fatty acid profile, the two-component regulatory systems, anti-sense transcription, the role played by rpsU genes in the translation process, etc. The genome-wide analysis of W-6 provided a deeper understanding of cold-adapted strategies of bacteria in environments. We elucidated the adaptive mechanism of the psychrophilic W-6 strain for survival in a cold environment, which provided a basis for further study on host-phage coevolution.

Microbial-driven carbon fixation in natural wetland.

With the development of global industrialization, carbon neutrality has become an issue that we must be paid attention to. Microorganisms not only have an important impact on the carbon chemical cycle between the Earth's biosphere and biogeography but also play a key role in maintaining the global organic carbon balance. Wetlands are the main reservoir of organic carbon in the mainland of China, and wetland carbon sinks are indispensable for China to achieve the goal of "dual carbon," and China has taken the consolidation and improvement of wetland carbon sink capacity as an important part of the carbon peaking action plan. As a unique low-latitude, high-altitude seasonal plateau wetland in China, Napahai shows high research value. However, the role of microbes in maintaining dissolved organic carbon balance in this area has not been reported. In the study, six carbon fixation genes, accA, aclB, acsA, acsB, cbbL, and rbcL, were analyzed based on metagenomics to elucidate the rich genetic diversity, uniqueness and differences in the Napahai plateau wetland. It was found that the microbial diversity in the Napahai plateau wetland was different from other habitats. In addition, the aclB gene, a rare taxon with high genetic diversity and rich species in the Napahai plateau wetland, played a key role in the microbial metabolic pathway. Finally, the construction of a metabolic pathway through the Kyoto encyclopedia for genes and genomes revealed the contribution of microbes to carbon fixation and the role of microbes in maintaining the organic carbon balance of the Napahai plateau wetland.

Facile hydrothermal synthesis of N-doped fluorescent carbon dots for selective detection of insecticide parathion.

Pesticides are enormously important to industry requirements and in agriculture for improving yields. Parathion is widely used to control pests in vegetables, fruits, and flowers. However, excessive use of parathion poses a threat to food safety, the environment, and human health. Due to low cost, ease to use, and high selectivity and sensitivity, a fluorescent nanoprobe is a candidate for parathion detection. Blue fluorescent carbon dots were prepared by a hydrothermal method with rutinum and o-phenylenediamine as precursors. The Rut-CDs were purified by using dialysis, thin layer chromatography, and a chromatographic column. Excellent linear ranges of 0-7.5 µg L-1 and 12.5-62.5 µg L-1 parathion were obtained with a low detection limit of 0.11 ng mL-1. In addition, the quenching mechanism of parathion to the fluorescence of Rut-CDs was illuminated. Furthermore, the nanoprobe was efficiently applied to determine the parathion content in Chinese cabbage, cantaloupe, and cowpea samples. It shows great potential to detect parathion.

Endophytic Fungal Community of Stellera chamaejasme L. and Its Possible Role in Improving Host Plants' Ecological Flexibility in Degraded Grasslands.

Stellera chamaejasme L. is a widely distributed poisonous plant in Chinese degraded grasslands. To investigate the role of endophytic fungi (EF) in S. chamaejasme's quick spread in grasslands, the endophytic fungal community of S. chamaejasme was studied through culture-dependent and culture-independent methods, and the plant-growth-promoting (PGP) traits of some culturable isolates were tested. Further, the growth-promoting effects of 8 isolates which showed better PGP traits were evaluated by pot experiments. The results showed that a total of 546 culturable EF were isolated from 1114 plant tissue segments, and the colonization rate (CR) of EF in roots (33.27%) was significantly higher than that in shoots (22.39%). Consistent with this, the number of specific types of EF was greater in roots (8 genera) than in shoots (1 genus). The same phenomenon was found in culture-independent study. There were 95 specific genera found in roots, while only 18 specific genera were found in shoots. In addition, the dominant EF were different between the two study methods. Cladosporium (18.13%) and Penicillium (15.93%) were the dominant EF in culture-dependent study, while Apiotrichum (13.21%) and Athelopsis (5.62%) were the dominant EF in culture-independent study. PGP trait tests indicated that 91.30% of the tested isolates (69) showed phosphorus solubilization, IAA production, or siderophores production activity. The benefit of 8 isolates on host plants' growth was further studied by pot experiments, and the results indicated that all of the isolates can improve host plants' growth. Among them, STL3G74 (Aspergillus niger) showed the best growth-promotion effect; it can increase the plant's shoot and root dry biomass by 68.44% and 74.50%, respectively, when compared with the controls. Our findings revealed that S. chamaejasme has a wide range of fungal endophytic assemblages, and most of them possess PGP activities, which may play a key role in its quick spread in degraded grasslands.

Genetic diversity of virus auxiliary metabolism genes associated with phosphorus metabolism in Napahai plateau wetland.

Viruses play important roles in ecosystems by interfering with the central metabolic pathways of the host during infection via the expression of auxiliary metabolic genes (AMGs), altering the productivity of ecosystems and thus affecting geochemical cycling. In this study, the genetic diversity of phosphorus metabolism AMGs phoH, phoU and pstS was investigated by phylogenetic analysis, PCoA analysis, and alpha diversity analysis based on metagenomic data. It was found that the majority of the sequences were unique to Napahai plateau wetland. It was shown that the genetic diversity of phoH, phoU and pstS genes was independent of both habitats and host origins. In addition, the metabolic pathway of AMGs associated with the phosphorus cycling was identified based on metagenomic data. When phosphorus is deficient, virus utilizes AMGs to affect the metabolic pathway, contributing to higher phosphorus levels in the host and facilitating virus survival, replication, and propagation in the host cell.

Biogeochemical sulfur cycling of virus auxiliary metabolic genes involved in Napahai plateau wetland.

Virus plays important roles in regulating microbial community structure, horizontal gene transfer, and promoting biological evolution, also augmenting host metabolism during infection via the expression of auxiliary metabolic genes (AMGs), and thus affect biogeochemical cycling in the oceans. As the "kidney of the earth," wetlands have rich biodiversity and abundant resources. Based on metagenomic data, 10 AMGs associated with sulfur cycling, i.e., tusA, moaD, dsrE, soxA, soxB, soxC, soxD, soxX, soxY, and soxZ, were analyzed in Napahai plateau wetland. The phylogenetic trees of AMGs involved in sulfur metabolism from different habitats and host origins were constructed. Combined with principal coordinate analysis, it revealed that most AMGs associated with sulfur metabolism clustered separately, indicating the abundance and uniqueness in this region. The sulfur metabolism pathways involved by AMGs were mainly SOX systems, among which sulfur oxidation was associated with moaD and dsrE genes, while sulfur transport was related to tusA genes. It provides an insight into the biogeochemical sulfur cycling in plateau wetlands and lays the foundation for further study on the co-evolution of virus and host.

Bioelectrocatalysis for CO2 reduction: recent advances and challenges to develop a sustainable system for CO2 utilization.

Activation and turning CO2 into value added products is a promising orientation to address environmental issues caused by CO2 emission. Currently, electrocatalysis has a potent well-established role for CO2 reduction with fast electron transfer rate; but it is challenged by the poor selectivity and low faradic efficiency. On the other side, biocatalysis, including enzymes and microbes, has been also employed for CO2 conversion to target Cn products with remarkably high selectivity; however, low solubility of CO2 in the liquid reaction phase seriously affects the catalytic efficiency. Therefore, a new synergistic role in bioelectrocatalysis for CO2 reduction is emerging thanks to its outstanding selectivity, high faradic efficiency, and desirable valuable Cn products under mild condition that are surveyed in this review. Herein, we comprehensively discuss the results already obtained for the integration craft of enzymatic-electrocatalysis and microbial-electrocatalysis technologies. In addition, the intrinsic nature of the combination is highly dependent on the electron transfer. Thus, both direct electron transfer and mediated electron transfer routes are modeled and concluded. We also explore the biocompatibility and synergistic effects of electrode materials, which emerge in combination with tuned enzymes and microbes to improve catalytic performance. The system by integrating solar energy driven photo-electrochemical technics with bio-catalysis is further discussed. We finally highlight the significant findings and perspectives that have provided strong foundations for the remarkable development of green and sustainable bioelectrocatalysis for CO2 reduction, and that offer a blueprint for Cn valuable products originate from CO2 under efficient and mild conditions.

Hybrid histidine kinase HisK2301 modulates carotenoid production to counteract cold-induced oxidative stress in Rhodosporidium kratochvilovae YM25235 under low temperature.

Hybrid histidine kinases (HHKs) are major sensor proteins for fungi that contribute to stress tolerance. In the present work, we investigated the roles and mechanisms of the HHK HisK2301 in cold-adapted Rhodosporidium kratochvilovae strain YM25235. The HisK2301 deletion strain was constructed by homologous recombination method and arranged for multiple stress tests. We analysed the content of carotenoid using UV-Vis and HPLC. Relative transcript levels of genes phytoene desaturase (RKCrtI) and phytoene synthase and lycopene cyclase (RKCrtYB) were analysed by RT-qPCR. Intracellular reactive oxygen species (ROS) generation was measured using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Our results clearly indicated that YM25235 produces γ-carotene, torulene, ß-carotene and torularhodin, with the latter two components strongly related to adapt to cold. HisK2301 is crucial for YM25235 adaptation to different types of stress such as cold, salt, osmotic and oxidative stress. Growth at low temperature clearly induced oxidative stress in YM25235, as more ROS accumulated at cold. During cold stress, HisK2301 is suggested to sense cold-induced ROS signals and then promote carotenoid production partially by RKCrtI and RKCrtYB to scavenge excessive ROS production. Such an inducible protective system may confer YM25235 fast response and better adaptation to cold stress. To conclude, our findings give the first insight into the effect of HisK2301 on carotenoid biosynthesis and cold-induced oxidative stress in fungi under low temperature and suggest the potential use of the cold-adapted HHK HisK2301 in industrial production of carotenoid.