Applied Microbiology and Biotechnology最新文献

{"title":"Colorectal cancer biofilm composition reveals distinct bacterial species signature.","authors":"Manish Kushwaha, Nishu Dalal, Shubham Chaudhary, Anam Ahmed, Govind K Makharia, Akhilesh Kumar Singh, Anil Kumar","doi":"10.1007/s00253-025-13537-8","DOIUrl":"10.1007/s00253-025-13537-8","url":null,"abstract":"<p><p>Human colon hosts a highly organized protective microbial ecosystem in the form of biofilms, increasingly recognized as key contributors to colorectal cancer (CRC) progression through microbial dysbiosis and complex host-microbiota interactions. In India, CRC ranks among the top ten cancers, with an age-standardized incidence rate of approximately 6.3 per 100,000 in males and 3.7 per 100,000 in females highlighting a higher risk in men, late-stage diagnosis, inadequate screening, and treatment limitations, particularly in urban populations. This study aims to explore the microbial composition of colonic biofilms from the Indian cohort of colorectal cancer patients from New Delhi, which is witnessing a rise in the incidence of CRC. Colorectal biopsies were taken from tumors (n = 15) and adjacent non-tumor tissues (n = 15) at the Gastrointestinal Department of AIIMS, New Delhi, India. Fluorescence in situ hybridization (FISH) was employed to determine the bacterial population in the biofilm. The workflow included microtomy, deparaffinization, tissue permeabilization, and hybridization with bacterial 16S rDNA probes, and the detected signals were visualized by confocal microscopy. The results showed quite different microbial patterns and tumor-associated biofilms were found to have an increased density of Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis, while Fusobacterium nucleatum and E. coli (pks⁺) with a pks⁺ genomic island encoding the genotoxin colibactin were seen less often. These results confirm significant dysbiosis and the formation of invasive biofilms in CRC tissues. Understanding the composition of these biofilms may facilitate the development of targeted strategies to restore microbial balance and reduce CRC risk both in the Indian and global population. KEY POINTS: • Tumor-associated biofilms show distinct microbial dysbiosis in Indian CRC patients. • Enrichment of Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis was observed at tumor site. • Insights into biofilm composition may aid to targeted interventions for CRC risk reduction.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"159"},"PeriodicalIF":3.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Borrelia surface proteins: new horizons in Lyme disease diagnosis.","authors":"Pauline Trezel, Mickaël Guérin, Hugo Da Ponte, Irene Maffucci, Stéphane Octave, Bérangère Avalle, Séverine Padiolleau-Lefèvre","doi":"10.1007/s00253-025-13490-6","DOIUrl":"10.1007/s00253-025-13490-6","url":null,"abstract":"<p><p>Spirochetes of the genus Borrelia are the causative agents of vector-borne diseases, including Lyme borreliosis (LB). Clinical LB diagnosis is challenging due to the heterogeneous and nonspecific symptoms among patients further complicated by the potential for co-infection with Borrelia species and other pathogens. Current diagnosis is based on an indirect serological approach with limitations such as early-stage low sensitivity and cross reactivity. This review explores the potential of Borrelia surface proteins as biomarkers for a more accurate diagnosis of LB, with a particular interest in proteins involved in (i) tissue adhesion, essential for host colonization, (ii) antigenic variation, and (iii) immune evasion. By detailing the role of the distinct surface proteins, the review highlights their potential as biomarkers in order to improve the detection of LB, particularly in the early stages. In addition to their diagnostic value, they also represent potential targets for the development of new therapeutic strategies. KEYPOINTS: • Various Borrelia surface proteins drive host colonization and immune evasion. • Novel bacterial proteins biomarkers are needed for improved diagnosis and therapy. • State of the art on Borrelia surface proteins and their associated role.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"156"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional proteomic analysis of Streptomyces sp. F-3 reveals its potential to effectively degrade waste-yeast.","authors":"Mengyu Liu, Shuxia Huang, Peng Yan, Xiuyun Wu, Hua Yin, Lushan Wang","doi":"10.1007/s00253-025-13541-y","DOIUrl":"10.1007/s00253-025-13541-y","url":null,"abstract":"<p><p>Streptomyces are renowned in pharmaceutical and medical fields for their ability to produce antibiotics and other bioactive secondary metabolites. In order to reduce industrial production costs, it is crucial to find suitable and cheaper raw materials as carbon and nitrogen sources for microbial growth processes. This study investigated the substrate preference of Streptomyces sp. F-3 using functional proteomic analysis. Streptomyces sp. F-3 exhibited varying degradation and utilization rates for different nitrogen source. The results indicated that the strain F-3 could not efficiently degrade intact globular proteins, but preferred to degrade peptone or protein hydrolysate, especially for waste-yeast. The strain F-3 could utilize waste-yeast to grow rapidly and produced a large amount of extracellular protein. The substrate-binding patterns of three S8 proteases secreted by Streptomyces sp. F-3 determined the nitrogen source degradation preference of the strain. In addition, the strain F-3 could secrete large amounts of β-glucanase and chitinase to utilize cell wall polysaccharides. Thus, waste-yeast, rich in peptone, β-glucan, and chitin, could be the superior substrate for culturing Streptomyces. This study not only broadens the application scenarios for waste-yeast, but also provides valuable insights for rapid and cost-effective industrial microbial cultivation. KEY POINTS: The substrate preference of Streptomyces sp. F-3 was analyzed by integrative omics. Structural omics revealed the hydrolysis specificity of S8 proteases from F-3. Waste-yeast served as the superior substrate for culturing Streptomyces.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"157"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a latex immunochromatography for detecting bovine early pregnancy-related glycoproteins.","authors":"Linlin Gu, Weiwei Wang, Mingjie Yang, Yafang Yu, Hui Chen, Kang Zhang, Kehu Yuan, Hui Fu, Qiuhua Mo, Bo Yang","doi":"10.1007/s00253-025-13542-x","DOIUrl":"10.1007/s00253-025-13542-x","url":null,"abstract":"<p><p>Early pregnancy diagnosis in dairy cows is an important part of the production processes. Accurate early pregnancy diagnosis can help veterinarians identify open cow as soon as possible and carry out the second breeding earlier, which is of great significance for improving reproductive efficiency of dairy cow. In this study, a rapid immunochromatography based on latex microspheres for detecting pregnancy-related glycoprotein (PAG) was established with two monoclonal antibodies. The samples collected from 28 days after breeding of 559 Holstein cows were used to diagnose pregnancy. The results showed that the minimum detection limit of the established latex immunochromatography for PAG was 0.2 ng/mL. Compared to ultrasound, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of this method for pregnancy diagnosis was 99.25%, 90%, 91.03%, 99.15%, and 94.68%, respectively, and the kappa value is 0.89, which demonstrated that the pregnancy diagnosis results of the test strip method have high consistency with ultrasound. Compared with commercial enzyme-linked immunosorbent assay (ELISA) kits, the positive coincidence rate, negative coincidence rate, and overall coincidence rate of this method was 98.29%, 97.6%, and 98.03%, respectively. This indicated that the test strip has high consistency with the currently widely used ELISA immunological diagnostic method. The latex immunochromatographic method established in this study can accurately diagnose pregnant cows and can be used for early pregnancy diagnosis of dairy cows. The method is simple to operate and fast to detect, and the results are easy to interpret, which is of great significance and clinical application value for cow early pregnancy detection. KEY POINTS: • A rapid immunochromatography based on latex microspheres with two monoclonal antibodies specific to PAG2 was established for early pregnancy diagnosis of dairy cows. • The early pregnancy test method, which we have developed, exhibits high sensitivity and can be utilized in small to medium-scale ranches. • The clinical sample test results demonstrated that the test strip has a high degree of consistency with ultrasound.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"155"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nipah virus: pathogenesis, genome, diagnosis, and treatment.","authors":"Rishav Madhukalya, Urvashi Yadav, Hilal Ahmad Parray, Nisha Raj, Santhik Subhasingh Lupitha, Vivek Kumar, Anjali Saroj, Vidushi Agarwal, Dilip Kumar, Supratik Das, Rajesh Kumar","doi":"10.1007/s00253-025-13474-6","DOIUrl":"10.1007/s00253-025-13474-6","url":null,"abstract":"<p><p>The highly infectious Nipah virus (NiV) is classified under the Paramyxoviridae family and is categorized under the genus Henipavirus. NiV spreads to humans through zoonotic transmission from reservoir host bats and other intermediate hosts. It is highly contagious and has a high case fatality rate (CFR) of ~ 40-80%. Only sporadic outbreaks have been reported so far, but like SARS-CoV2, NiV has a high pandemic potential and has been put on the World Health Organization (WHO) priority pathogen list. Currently, no clinically approved antivirals, immunotherapy, or vaccines are available to tackle NiV infection, thereby necessitating further research into its life cycle, transmission, and pathogenesis. This detailed review outlines the origin and spread of the Nipah virus, its modes of transmission, risk factors, its genome, key proteins, pathogenesis, and clinical features. We also discuss different diagnostic approaches and ongoing research to develop therapies ranging from antibodies to vaccines. KEY POINTS: •Pandemic preparedness for emerging and re-emerging viruses. •Novel approaches for diagnostics and therapeutics for Nipah viruse. •Global threat from biosafety level 4 pathogens. •Animal models for Nipah virus research.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"158"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Sanghuangporus sanghuang for enhanced (-)-aristolone production via metabolic pathway optimization and terpene synthase engineering.","authors":"Yihan Li, Chuanzhi Kang, Jiahui Xu, Wenqing Zhou, Weishan Pan, Daofang Xia, Jian Liang, Lanping Guo, Xiao-Kui Ma","doi":"10.1007/s00253-025-13540-z","DOIUrl":"10.1007/s00253-025-13540-z","url":null,"abstract":"<p><p>(-)-Aristolone, a sesquiterpene with promising therapeutic properties such as antidiabetic and vasorelaxant effects, currently suffers from limited availability due to inefficient chemical synthesis and lack of viable extraction methods. This study presents a novel strategy for high-yield microbial (-)-aristolone production using Sanghuangporus sanghuang DM989 as a fungal chassis. Genome mining identified nine sesquiterpene synthases, among which TPS2152 was functionally linked to (-)-aristolone biosynthesis. TPS2152 harbors a rare DQxxD motif, diverging from the canonical DDxxD motif in plants, suggesting unique catalytic properties in fungi. Overexpression of farnesyl pyrophosphate synthase (FPPS) increased FPP precursor supply, resulting in a 78.79% rise in squalene content (1.18 mg/g) and enabling de novo (-)-aristolone synthesis (0.42 mg/g) in the FPPS⁺ strain. To enhance FPP flux toward (-)-aristolone, the ΔSQS/TPS2152⁺ strain was constructed by co-overexpressing TPS2152 and silencing squalene synthase (SQS), yielding a 210% increase in (-)-aristolone (1.30 mg/g) and 56.78% reduction in squalene compared to FPPS⁺. Further, site-directed mutagenesis converted DQxxD to DDxxD, producing TPS2152D, which retained substrate binding affinity (docking score: - 9.1 kcal/mol) and exhibited a 2.57-fold increase in catalytic efficiency. Integration of TPS2152D with SQS silencing produced the ΔSQS/TPS2152D⁺ strain, achieving a 217% higher (-)-aristolone yield than FPPS⁺. Fermentation kinetics showed product accumulation from day 5, with maximal Q_p on days 8 and complete squalene suppression by day 9. These results establish S. sanghuang as a robust microbial platform for sesquiterpene production and demonstrate the feasibility of combining fungal pathway engineering and motif-based enzyme optimization for scalable biosynthesis of high-value terpenoids.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"154"},"PeriodicalIF":3.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of nanozyme thixotropic anionic hydrogel for treating fungal keratitis by Dectin-1/p38 pathway.","authors":"Chenchen Zhang, Jia Li, Xinyue Shen, Jihong Wang","doi":"10.1007/s00253-025-13529-8","DOIUrl":"10.1007/s00253-025-13529-8","url":null,"abstract":"<p><p>Fungal keratitis (FK) is a major cause of corneal blindness, particularly in China, where treatment is often limited by systemic side effects and antifungal drug resistance. We propose a nanozyme (carbon nanotube (CNT))-based anionic hydrogel coating (NHC) loaded with itraconazole (IZ) (NTH@CNT/IZ) as a treatment for FK to overcome these challenges. This formulation was designed to enhance ocular drug delivery, improve antifungal efficacy, and reduce inflammation. In vitro assays against Aspergillus fumigatus demonstrated potent antifungal activity, including significant reductions in colony-forming units and biofilm formation at 50 µg/mL. Cell viability tests using ARPE-19 cells revealed high biocompatibility, with no observed morphological alterations or apoptosis, despite increased ROS and DNA proliferative activity. Importantly, NTH@CNT/IZ markedly downregulated inflammatory mediators-Dectin-1, IL-1β, and TNF-α-and inhibited phosphorylation of p38 MAPK, indicating suppression of the Dectin-1/p38 MAPK signaling pathway. In vivo results further confirmed its therapeutic potential, showing reduced corneal fungal burden and inflammation, along with effective penetration through the corneal epithelium, overcoming mucosal and fungal barriers. Together, these findings highlight NTH@CNT/IZ as a promising localized treatment strategy for fungal keratitis, offering targeted antifungal action and immune modulation to improve clinical outcomes and preserve ocular integrity. KEY POINTS: Nanozyme hydrogel for ocular health In vitro antifungal efficacy.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"153"},"PeriodicalIF":3.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl-alcohol oxidases: catalysis, diversity, structure-function and emerging biotechnological applications.","authors":"Paula Cinca-Fernando, Aurora Vázquez-Rodríguez, Juan Mangas-Sánchez, Patricia Ferreira","doi":"10.1007/s00253-025-13538-7","DOIUrl":"10.1007/s00253-025-13538-7","url":null,"abstract":"<p><p>Aryl-alcohol oxidases (AAOs) are flavin-dependent enzymes of the glucose-methanol-choline (GMC) oxidoreductase superfamily that catalyze the oxidation of a broad range of activated primary alcohols into their corresponding aldehydes, generating hydrogen peroxide. While traditionally studied in wood-decaying fungi, AAOs have recently been identified in bacteria and arthropods, revealing unexpected structural and functional diversity. These enzymes display broad substrate promiscuity, with preferences shaped by differences in active-site architecture and physicochemical properties. Structural studies across kingdoms show a conserved GMC fold with specific adaptations in substrate-binding domains. Detailed mechanistic insights-particularly from the AAO from Pleurotus eryngii-suggest a consensus hydride transfer mechanism involving conserved histidine residues, enabling both oxidase and dehydrogenase activity. To explore AAO diversity, BLAST-based mining was performed across fungal, bacterial, and arthropod genomes, leading to the identification and classification of hundreds of putative AAO sequences. These have been further grouped into distinct structural and evolutionary types based on conserved motifs and active-site architecture, revealing convergent strategies and potential functional specialization across kingdoms. Beyond their natural role in biomass degradation, AAOs hold significant biotechnological potential in green chemistry, including the synthesis of valuable aldehydes, bioplastics precursors like 2,5-furandicarboxylic acid, and applications in asymmetric synthesis. Recent advances demonstrate the feasibility of integrating AAOs into industrial biocatalytic processes and artificial cascades. This growing understanding of AAO diversity, structure-function relationships, and biotechnological applications paves the way for the development of novel sustainable biocatalysts in chemical, pharmaceutical, and material industries. KEY POINTS: Aryl-alcohol oxidases (AAOs) occur across fungi, bacteria, and arthropods, with distinct structural and functional features. Sequence similarity searches reveal diverse AAO types with distinct structural and evolutionary traits. AAOs enable green synthesis of high-value-added bio-based chemicals.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"151"},"PeriodicalIF":3.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The phenomenon of anhydrobiosis-structural and functional changes in yeast cells.","authors":"Marek Kieliszek","doi":"10.1007/s00253-025-13539-6","DOIUrl":"10.1007/s00253-025-13539-6","url":null,"abstract":"<p><p>Anhydrobiosis is a phenomenon that involves the ability of microorganisms to survive in an environment of virtually complete dehydration. Yeast cells in anhydrobiosis exhibit several structural and functional changes. Survival of such extreme environmental conditions while maintaining the viability of eukaryotic cells after rehydration is a subject of constant interest in the scientific community worldwide. This review article presents the most essential information discussing the effect of dehydration on several structural and functional changes occurring in yeast cell organelles. It is worth emphasizing that at the cellular level, in dehydration conditions, it is possible to observe the occurrence of processes responsible for cytoplasm condensation, cytoskeleton reorganization or changes in the structure of the cell membrane and individual organelles. In addition, protein aggregation and a reduction in metabolic activity also occur. The consequence of such processes is the inhibition of the cell cycle and a decrease in the activity of individual enzymes. One of the key mechanisms responsible for yeast defense against this phenomenon is the accumulation of protective substances. Understanding the functioning of complex adaptive mechanisms of yeast cells occurring in the state of anhydrobiosis will constitute an extension of the current knowledge in this scientific field. It is worth emphasizing that conducting future research on explaining the complex relationships that occur at the molecular level in the cytosol of yeast cells between individual organelles will provide new molecular clues covering the functioning of particular signaling pathways. At the same time, using knowledge from this technological sector will be an opportunity to develop innovative technologies in the field of designing yeast-derived products. KEY POINTS: • Yeast cells exhibit significant structural and functional changes in the anhydrobiosis state. • Dehydration leads to cytoskeleton reorganization, membrane changes, and cytoplasmic condensation. • Anhydrobiosis leads to protein aggregation and reduced translation at the ribosome level in yeast.</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"152"},"PeriodicalIF":3.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple regulators control the biosynthesis of brasilicardin in Nocardia terpenica.","authors":"Marcin Wolański, Michał Krawiec, Kay Nieselt, Tobias Schwarz, Dilek Dere, Bernhard Krismer, Carolina Cano-Prieto, Harald Gross, Jolanta Zakrzewska-Czerwińska","doi":"10.1007/s00253-025-13485-3","DOIUrl":"10.1007/s00253-025-13485-3","url":null,"abstract":"<p><p>Brasilicardin A, BraA, is a secondary metabolite produced by the bacterium Nocardia terpenica, and a promising drug due to its potent immunosuppressive activity and low cytotoxicity. Currently, a semisynthetic approach confers the production of a complete compound but suffers from limited heterologous biosynthesis of BraA intermediates used in the chemical semi-synthesis steps leading to only lab-scale quantities of the compound. A better understanding of the gene expression regulatory pathways involved within the brasilicardin biosynthetic gene cluster, Bra-BGC, is a prerequisite to improving production titers further. However, the transcriptional regulation of the Bra-BGC has only been superficially analyzed, till now. In this study, we comprehensively analyze the functions of several unstudied transcriptional regulators, KstR, SdpR, and OmpR, encoded within the close vicinity of the Bra-BGC, and delve into the role of the previously described cluster-situated activator Bra12. We present that Bra12 and the novel regulator SdpR bind several DNA sequences located in the promoter regions of the genes essential for BraA biosynthesis. Subsequently, we demonstrate the complex regulatory network through which both regulators can control the activity of those gene promoters and thus gene expression in Bra-BGC. Furthermore, using the heterologous producer strain Amycolatopsis japonicum, we present that Bra12 and SdpR regulators play opposite roles in brasilicardin congener biosynthesis. Finally, we propose a comprehensive model of multilevel gene expression regulation in Bra-BGC and propose the roles of locally encoded transcriptional regulators. KEY POINTS: • Multiple regulators bind within the brasilicardin gene cluster. • Bra12 and SdpR are key regulators of brasilicardin biosynthesis. • The bra0 - 1 intergenic region is likely a key regulatory \"hot-spot.\"</p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":"150"},"PeriodicalIF":3.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}