Structural and Functional Basis of GenB2 Isomerase Activity from Gentamicin Biosynthesis.

Aminoglycosides are essential antibiotics used to treat severe infections caused mainly by Gram-negative bacteria. Gentamicin is an aminoglycoside and, despite its toxicity, is clinically used to treat several pulmonary and urinary infections. The commercial form of gentamicin is a mixture of five compounds with minor differences in the methylation of one of their aminosugars. In the case of two compounds, gentamicin C2 and C2a, the only difference is the stereochemistry of the methyl group attached to C-6'. GenB2 is the enzyme responsible for this epimerization and is one of the four PLP-dependent enzymes encoded by the gentamicin biosynthetic gene cluster. Herein, we have determined the structure of GenB2 in its holo form in complex with PMP and also in the ternary complex with gentamicin X2 and G418, two substrate analogues. Based on the structural analysis, we were able to identify the structural basis for the catalytic mechanism of this enzyme, which was also studied by site-directed mutagenesis. Unprecedently, GenB2 is a PLP-dependent enzyme from fold I, which is able to catalyze an epimerization but with a mechanism distinct from that of fold III PLP-dependent epimerases using a cysteine residue near the N-terminus. The substitution of this cysteine residue for serine or alanine completely abolished the epimerase function of the enzyme, confirming its involvement. This study not only contributes to the understanding of the enzymology of gentamicin biosynthesis but also provides valuable details for exploring the enzymatic production of new aminoglycoside derivatives.

Clinical evaluation of enhanced recovery versus conventional care in the perioperative period for intradural extramedullary spinal tumors: a study protocol for a multicenter, randomized controlled trial.

BACKGROUND: This randomized clinical trial protocol aimed to investigate the comparative efficacy of an enhanced recovery after surgery (ERAS) protocol versus traditional perioperative care programs in patients with intradural extramedullary spinal tumors. METHODS: The study included 180 patients aged 18-80 years, who were randomly assigned to two groups: Group A receiving traditional perioperative care and Group B receiving accelerated rehabilitation perioperative care. The nurse responsible for patient care was informed of the group assignment, but the patients themselves remained blinded to the intervention. The primary outcome measure was the Karnofsky Performance Scale score, which assessed functional status. The secondary outcomes included the Japanese Orthopedic Association Scale, Numeric Pain Rating Scale, length of postoperative hospital stay, duration of urethral catheterization, patient satisfaction questionnaire, and complication rates. Follow-up assessments were conducted telephonically 1 month, 3 months, and 6 months after the surgery. DISCUSSION: This study protocol provided a structured approach to assess the potential benefits of ERAS during the perioperative period for patients with intradural extramedullary tumors, aiming to improve patient outcomes and overall care efficiency. TRIAL REGISTRATION: This study has been registered with the China Clinical Trials Registry (Project No: ChiCTR2200063347). Registered on September 5 2022.

Rare primary colonic T cell lymphoma with curative resection by endoscopic submucosal dissection: A case report.

BACKGROUND: The gastrointestinal tract is a well-known extranodal site of lymphoma. B-cell lymphoma is the most common type, while T-cell lymphoma is uncommon. Primary gastrointestinal lymphoma mainly occurs in the stomach and small intestine, and the colon is less frequently involved, especially in females. CASE SUMMARY: A 45-year-old woman was admitted to our hospital for physical examination. Gastroenteroscopy revealed a visible pedunculated polyp in the transverse colon, for which endoscopic submucosal dissection (ESD) was performed. Pathology suggested highly active proliferation of T lymphocytes with atypical hyperplasia. CONCLUSION: A middle-aged female patient was found to have colonic T-cell lymphoma by endoscopy. The lesion was successfully removed by ESD, and the surgical margin was negative. It is essential to raise awareness of colonic T-cell lymphoma and choose the appropriate treatment.

Engineered cytosine base editor enabling broad-scope and high-fidelity gene editing in Streptomyces.

Base editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes and prokaryotes. For Streptomyces, renowned as one of the most prolific bacterial producers of antibiotics, the challenges are more pronounced due to its diverse genomic content and high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with both high efficiency and -fidelity for Streptomyces. Of note, eSCBE3-NG-Hypa recognizes NG PAM and exhibits high activity at challenging sites with high GC content or GC motifs, while displaying minimal off-target effects. To illustrate its practicability, we employ eSCBE3-NG-Hypa to achieve precise key amino acid conversion of the dehydratase (DH) domains within the modular polyketide synthase (PKS) responsible for the insecticide avermectins biosynthesis, achieving domains inactivation. The resulting DH-inactivated mutants, while ceasing avermectins production, produce a high yield of oligomycin, indicating competitive relationships among multiple biosynthetic gene clusters (BGCs) in Streptomyces avermitilis. Leveraging this insight, we use eSCBE3-NG-Hypa to introduce premature stop codons into competitor gene cluster of ave in an industrial S. avermitilis, with the mutant Δolm exhibiting the highest 4.45-fold increase in avermectin B1a compared to the control. This work provides a potent tool for modifying biosynthetic pathways and advancing metabolic engineering in Streptomyces.

Preparation of a self-matting, anti-fingerprint and skin-tactile wood coating via biomimetic self-wrinkling patterns.

Inspired by natural wrinkled surfaces, artificial surfaces with biomimetic wrinkled structures have been widely used to improve optical properties, wettability, and antibacterial properties. However, the preparation of wrinkled structures has the disadvantages of long-time consumption and complex processes. Herein, we prepared a self-wrinkling polyurethane-acrylate (PUA) wood coating via biomimetic self-wrinkling patterns by using a light-emitting diode (LED)/excimer/mercury lamp curing system, which was capable of self-matting, anti-fingerprint and skin-tactile performance. By adjusting the irradiation intensity in the curing system, the wavelength (λ) and amplitude (A) of wrinkles on the coating surface were controlled to enhance the coating performance. After curing by the LED, excimer, and mercury lamps at energy intensities of 500, 30, and 300 mW/cm2 respectively, the self-wrinkling coating showed excellent surface performance. The self-wrinkling coating represented low gloss of 4.1 GU at 85°, high hardness of 4H. Interestingly, the coating surface had a high hydrophobicity (104.5°) and low surface energy (29-30 mN/m) and low coefficient (COF) of friction (0.1-0.2), which were consistent with those of the human skin surface. Besides, the wrinkled structure also improved the thermal stability of the coating samples. This study provided a promising technique for the mass production of self-wrinkling coatings that could be used in wood-based panels, furniture, and leather.

Immunomodulation in Endometriosis: Investigating the interrelationship between VISTA expression and Escherichia.Shigella-Associated metabolites.

AIMS: Endometriosis is characterized by an abnormal immune microenvironment. Despite the extensive use of immune therapies, the application of immune checkpoint inhibitors in endometriosis lacks confidence due to the instability of preclinical research data. This study aims to elucidate the regulation of the immune inhibitory checkpoint VISTA and its effects on T cells from the perspective of microbiota and metabolism. MAIN METHODS: We divided endometriosis patients into high and low groups based on the expression levels of VISTA in lesion tissues. We collected peritoneal fluid samples from these two groups and performed 16 s RNA sequencing and metabolomics analysis to investigate microbial diversity and differential metabolites. Through combined analysis, we identified microbial-associated metabolites and validated their correlation with VISTA and CD8 + T cells using ELISA and immunofluorescence. In vitro experiments were conducted to confirm the regulatory relationship among these factors. KEY FINDINGS: Our findings revealed a distinct correlation between VISTA expression and the microbial colony Escherichia.Shigella. Moreover, we identified the metabolites LTD4-d5 and 2-n-Propylthiazolidine-4-carboxylic acid as being associated with both Escherichia.Shigella and VISTA expression. In vitro experiments confirmed the inhibitory effects of these metabolites on VISTA expression, while they demonstrated a positive regulation of CD8 + T cell infiltration into endometriotic lesions. SIGNIFICANCE: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.

A robust, eco-friendly, and biodegradable cellulose nanofiber composite film for highly effective formaldehyde removal at room temperature.

Formaldehyde (HCHO) poses a significant threat as a common indoor air pollutant, leading to various health issues. However, effectively addressing HCHO removal at room temperature remains a considerable challenge. This paper presents the preparation of a robust, eco-friendly, and biodegradable composite cellulose nanofiber film, incorporating CeO2-Ag@MnO2 catalysts and TEMPO-oxidized cellulose nanofiber (TOCNF), for high-efficiency HCHO removal at room temperature. A CeO2-Ag@MnO2 ternary catalyst with a core-shell structure was constructed to enhance the catalytic oxidation activity and stability. This structure increased the number of active sites on the catalyst surface and enhanced the interfacial synergistic effect of Ce-Ag-Mn. The TOCNF physically adsorbed HCHO in the composite film, while the catalyst oxidized it to CO2 and water. The composite films, particularly those with 20 wt% CeO2-Ag@MnO2 catalyst, exhibited high HCHO removal rates of 91.2 % at 20 °C and 99.6 % at 60 °C. Furthermore, the TOCNF/20 CAM composite films demonstrated excellent mechanical properties and degradability. This composite film offers an efficient and eco-friendly solution for the catalytic oxidation of HCHO at room temperature.

Targeting lipid peroxidation-associated ferroptosis suppresses lung carcinoma progression by regulating cell cycle arrest.

Lung carcinoma is a frequently encountered cancerous growth that affects the respiratory tract and has a high occurrence rate globally. In light of the ongoing worldwide health emergency, the significance of efficient therapeutic agents and strategies is of utmost importance. A meticulous control of the cell cycle is crucial for comprehending the pathophysiology and molecular causes of lung cancer, as well as for the formulation of efficacious therapeutic medicines. The mechanism by which cells synchronize cell cycle with cell survival and death is still not fully understood. In this study, we demonstrate that the halting of the cell cycle has a strong inhibitory impact on ferroptosis, a specific type of controlled cell death triggered by excessive lipid peroxidation at the membranes of cells. Ferroptosis is halted through the mechanism of cell cycle arrest, which involves the deposition of intracellular lipids mediated by diacylglycerol acyltransferase (DGAT). Excessive amounts of polyunsaturated fatty acids (PUFAs) are stored as triacylglycerols (TAGs) within inactive cells. As a result, inhibiting DGAT causes a rearrangement of PUFAs from TAGs to phospholipids and makes arrested cells more susceptible to ferroptosis. We demonstrate that certain lung cancer cells that are resistant to antimitotic drugs and have a slow-cycling behavior exhibit an increase in lipid droplets. Furthermore, we find that the growth of tumors resistant to 5-fluorouracil, lorlatinib, and docetaxel can be effectively suppressed by a combination treatment involving the use of ferroptosis inducers and DGAT inhibitors, which induces ferroptosis. Collectively, these findings demonstrate the involvement of cell cycle arrest in conferring resistance to ferroptosis and propose a potential therapeutic approach for addressing the challenge of slow-cycling malignancies that exhibit resistance to ferroptosis.

Exploring the Relevance of Disulfidptosis to the Pathophysiology of Ulcerative Colitis by Bioinformatics Analysis.

Background: Ulcerative colitis (UC) is a nonspecific inflammatory disease confined to the intestinal mucosa and submucosa, and its prevalence significantly increases each year. Disulfidptosis is a recently discovered new form of cell death that has been suggested to be involved in multiple diseases. The aim of this study was to explore the relevance of disulfidptosis in UC. Methods: First, the UC datasets were downloaded from the Gene Expression Omnibus (GEO) database, and UC samples were typed based on upregulated disulfidptosis-related genes (DRGs). Then, weighted gene co-expression network analysis (WGCNA) was performed on the datasets and molecular subtypes of UC, respectively, to obtain candidate signature genes. After validation of the validation set and qRT-PCR, we constructed a nomogram model by signature genes to predict the risk of UC. Finally, single-cell sequencing analysis was used to study the heterogeneity of UC and to demonstrate the expression of DRGs and signature genes at the single-cell level. Results: A total of 7 DRGs were significantly upregulated in the expression profiles of UC, and 180 UC samples were divided into two subtypes based on these DRGs. Five candidate signature genes were obtained by intersecting two key gene modules selected by WGCNA. After evaluation, four signature genes with diagnostic relevance (COL4A1, PRRX1, NNMT, and PECAM1) were eventually identified. The nomogram model showed excellent prediction ability. Finally, in the single-cell analysis, there were eight cell types (including B cells, T cells, monocyte, smooth muscle cells, epithelial cells, neutrophil, endothelial cells and NK cells) were identified. The signature genes were significantly expressed mainly in endothelial cells and smooth muscle cells. Conclusion: In this study, subtypes related to disulfidptosis were identified, and single-cell analysis was performed to understand the pathogenesis of UC from a new perspective. Four signature genes were screened and a prediction model with high accuracy was established. This provides novel insights for early diagnosis and therapeutic targets in UC.

Microbiome in gynecologic malignancies: a bibliometric analysis from 2012 to 2022.

Microbiome and microbial dysbiosis have been proven to be involved in the carcinogenesis and treatment of gynecologic malignancies. However, there is a noticeable gap in the literature, as no comprehensive papers have covered general information, research status, and research frontiers in this field. This study addressed this gap by exploring the relationship between the gut and female reproductive tract (FRT) microbiome and gynecological cancers from a bibliometric perspective. Using VOSviewer 1.6.18, CiteSpace 6.1.R6, and HistCite Pro 2.1 software, we analyzed data retrieved from the Web of Science (WOS) Core Collection (WoSCC) database. Our dataset, consisting of 204 articles published from 2012 to 2022, revealed a consistent and upward publication trend. The United States and the United Kingdom were the primary driving forces, attributed to their prolificacy, high-quality output, and extensive cooperation. The University of Arizona Cancer Center, which is affiliated with the United States, ranked first among the top ten most prolific institutions. Frontiers in Cellular and Infection Microbiology emerged as the leading publisher. Herbst-Kralovetz MM led as the most productive author. Mitra A was the most influential author. Cervical cancer is notably associated with the microbiome, while endometrial and ovarian cancers are receiving increased attention in the last year. Intersections between the gut microbiome and estrogen are of growing importance. Current research focuses on identifying specific microbial species for etiological diagnosis, while frontiers mainly focus on the anticancer potential of microorganisms, such as regulating the effects of immune checkpoint inhibitors. In conclusion, this study sheds light on a novel and burgeoning direction of research, providing a one-stop overview of the microbiome in gynecologic malignancies. Its findings aim to help young researchers to identify research directions and future trends for ongoing investigations.

Haplotype-resolved assembly of diploid and polyploid genomes using quantum computing.

Precision medicine's emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given its combinatorial nature. While classical algorithms have made strides in addressing this issue, the potential of quantum computing remains largely untapped. Here, we present the vehicle routing problem (VRP) assembler: an approach that transforms this task into a vehicle routing problem, an optimization formulation solvable on a quantum computer. We demonstrate its potential and feasibility through a proof of concept on short synthetic diploid and triploid genomes using a D-Wave quantum annealer. To tackle larger-scale assembly problems, we integrate the VRP assembler with Google's OR-Tools, achieving a haplotype-resolved local assembly across the human major histocompatibility complex (MHC) region. Our results show encouraging performance compared to Hifiasm with phasing accuracy approaching the theoretical limit, underscoring the promising future of quantum computing in bioinformatics.

Elucidation of genes enhancing natural product biosynthesis through co-evolution analysis.

Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the 'coenzyme' category have been examined, including a gene cluster encoding for the cofactor pyrroloquinoline quinone. When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides an innovative engineering strategy for improving polyketide production and finding previously unidentified BGCs.

Biomimetic design of micro- and nano-wrinkle wood surface via coating reinforced with hyperbranched polymer grafted cellulose nanofibers for skin-tactile performance.

Inspired from human skin, micro- and nano-wrinkled wood surface with skin-tactile performance was designed and developed using a waterborne UV-curable polyurethane acrylate coating and cellulose nofibers (CNF). To further improve the properties, the CNF was diacetylated to D-CNF and further grafted with a hyperbranched polymer containing rich end amino groups (HB-CNF). The surface structure and chemical reactions were characterized, and the skin-tactile performance of the coating was comprehensively investigated. The HB-CNF exhibited excellent dispersion in the coating, and extensive reactions occurred between the two through the -NH2 and terminal -NCO groups, resulting in much improved mechanical properties and durability. Micro-wrinkles with a width of approximately 12-15 µm and a height of 8-14 µm were created, and nano-protrusions of wrinkles ranging from to 50-100 nm were obtained. The coated surface was hydrophobic and exhibited high resilience after compression, with a gloss of 3.3 GU at an incident angle of 60° and a static friction coefficient of 0.26, both of which were similar to those of human skin. The results presented an effective strategy for high-performance wood products with a good feeling, which is helpful to improve the market competitiveness and meet the people's pursuit of a better life.

Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis.

INTRODUCTION: Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The mechanism of infertility caused by EM has not yet been consistently explained. In recent years, studies have shown a link between infertility associated with EM and changes in the reproductive tract microbiota. METHODS: In this study, we involved 26 EM patients (8 cases of stage I-II and 18 cases of stage III-IV) and 31 control subjects who were tubal obstruction-related infertility (TORI). The samples from peritoneal fluid (PF) and uterine fluid (UF) were collected and sequenced by 16 S rRNA amplicon. RESULTS: In the comparison of microbial diversity, we found no significant differences in the microbial diversity of PF and UF between patients with stage I-II EM and those with TORI. However, there was a significant difference in microbial diversity among patients with stage III-IV EM compared to the previous two groups. Lactobacillus decreased in PF of EM compared to the control group, while it increased in UF. In PF, the abundance of Pseudomonas, Enterococcus, Dubosiella and Klebsiella was significantly higher in patients with stage III-IV compared to TORI patients. And in UF, the main differences existed between stage I-II EM compared to the other two groups. The abundance of pontibacter, aquabacterium, Rikenellaceae and so on at the genus level was significantly enriched in the EM patients with stage I-II. In the analysis based on KEGG database, EM may affect the receptivity related pathways of the endometrium by influencing changes in the uterine microbiota. CONCLUSION: Our results indicated that as EM progresses, the microorganisms in UF and PF keep changing. These changes in the microbiota, as well as the resulting alternations in gene functional classification, may play an important role in the infertility associated with EM.

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Disrupted Tuzzerella abundance and impaired L-glutamine levels induce Treg accumulation in ovarian endometriosis: a comprehensive multi-omics analysis.

INTRODUCTION: The microbial community plays a crucial role in the pathological microenvironment. However, the structure of the microbial community within endometriotic lesions and its impact on the microenvironment is still limited. METHODS: All 55 tissue samples, including ovarian ectopic (OEMs) and normal (NE) endometrium, were subjected to 16S rRNA sequencing, metabolomic and proteomic analysis. RESULTS: We found the abundance of Tuzzerella is significantly lower in OEMs compared to NE tissue (p < 0.01). We selected samples from these two groups that exhibited the most pronounced difference in Tuzzerella abundance for further metabolomic and proteomic analysis. Our findings indicated that endometriotic lesions were associated with a decrease in L-Glutamine levels. However, proteomic analysis revealed a significant upregulation of proteins related to the complement pathway, including C3, C7, C1S, CLU, and A2M. Subsequent metabolic and protein correlation predictions demonstrated a negative regulation between L-Glutamine and C7. In vitro experiments further confirmed that high concentrations of Glutamine significantly inhibit C7 protein expression. Additionally, immune cell infiltration analysis, multiplex immunofluorescence, and multifactorial testing demonstrated a positive correlation between C7 expression and the infiltration of regulatory T cells (Tregs) in ectopic lesions, while L-Glutamine was found to negatively regulate the expression of chemotactic factors for Tregs. CONCLUSION: In this study, we found a clear multi-omics pathway alteration, "Tuzzerella (microbe)-L-Glutamine (metabolite)-C7 (protein)," which affects the infiltration of Tregs in endometriotic lesions. Our findings provide insights into endometriosis classification and personalized treatment strategies based on microbial structures.

Development and validation of a clinic-radiological model to predict tumor spread through air spaces in stage I lung adenocarcinoma.

OBJECTIVES: Tumor spread through air spaces (STAS) is associated with poor prognosis and impacts surgical options. We aimed to develop a user-friendly model based on 2-[18F] FDG PET/CT to predict STAS in stage I lung adenocarcinoma (LAC). MATERIALS AND METHODS: A total of 466 stage I LAC patients who underwent 2-[18F] FDG PET/CT examination and resection surgery were retrospectively enrolled. They were split into a training cohort (n = 232, 20.3% STAS-positive), a validation cohort (n = 122, 27.0% STAS-positive), and a test cohort (n = 112, 29.5% STAS-positive) according to chronological order. Some commonly used clinical data, visualized CT features, and SUVmax were analyzed to identify independent predictors of STAS. A prediction model was built using the independent predictors and validated using the three chronologically separated cohorts. Model performance was assessed using ROC curves and calculations of AUC. RESULTS: The differences in age (P = 0.009), lesion density subtype (P < 0.001), spiculation sign (P < 0.001), bronchus truncation sign (P = 0.001), and SUVmax (P < 0.001) between the positive and negative groups were statistically significant. Age ≥ 56 years [OR(95%CI):3.310(1.150-9.530), P = 0.027], lesion density subtype (P = 0.004) and SUVmax ≥ 2.5 g/ml [OR(95%CI):3.268(1.021-1.356), P = 0.005] were the independent factors predicting STAS. Logistic regression was used to build the A-D-S (Age-Density-SUVmax) prediction model, and the AUCs were 0.808, 0.786 and 0.806 in the training, validation, and test cohorts, respectively. CONCLUSIONS: STAS was more likely to occur in older patients, in solid lesions and higher SUVmax in stage I LAC. The PET/CT-based A-D-S prediction model is easy to use and has a high level of reliability in diagnosing.

Design and Engineering of Light-Induced Base Editors Facilitating Genome Editing with Enhanced Fidelity.

Base editors, which enable targeted locus nucleotide conversion in genomic DNA without double-stranded breaks, have been engineered as powerful tools for biotechnological and clinical applications. However, the application of base editors is limited by their off-target effects. Continuously expressed deaminases used for gene editing may lead to unwanted base alterations at unpredictable genomic locations. In the present study, blue-light-activated base editors (BLBEs) are engineered based on the distinct photoswitches magnets that can switch from a monomer to dimerization state in response to blue light. By fusing the N- and C-termini of split DNA deaminases with photoswitches Magnets, efficient A-to-G and C-to-T base editing is achieved in response to blue light in prokaryotic and eukaryotic cells. Furthermore, the results showed that BLBEs can realize precise blue light-induced gene editing across broad genomic loci with low off-target activity at the DNA- and RNA-level. Collectively, these findings suggest that the optogenetic utilization of base editing and optical base editors may provide powerful tools to promote the development of optogenetic genome engineering.

Methylation in hangtaimycin biosynthesis and its antibacterial activities.

About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug development. So, methyltransferases catalyzing the methylation have always attracted great attention. Hangtaimycin (HTM) is a potent hepatoprotective agent. Previous study showed that its biosynthetic gene cluster contained three methyltransferase domains, but their characteristics in HTM biosynthetic pathway has not been revealed. In this study, we clarified multi-methylations in HTM biosynthesis in vivo. It showed that the two S-adenosylmethionine-dependent methyltransferases (SAM-MTs) of HtmA2(-module 6)-MT domain and HtmB2(-module 18)-MT domain are responsible for the installation of methyl group at C-45 and N-12, respectively, whereas the FK506 methyltransferase (FKMT) type O-methyltransferase of HtmB1(-module 16)-MT domain take care of the methylation at O-21 of HTM. We also reported the antibacterial activities of HTM in this study, and found that it showed activities against M. luteus, B. thuringiensis and A. baumannii with MIC of 4 µg/mL, 4 µg/mL, and 64 µg/mL, respectively.