Molecular Biology Reports最新文献

{"title":"CRISPR/Cas9 in perspective: evaluating efficacy, delivery methods, and ethical challenges in genome editing.","authors":"Chandrajeet Dhara, Harsh Sah, Saumyatika Gantayat, Minakshi Rajput, Sudhanshu Mishra","doi":"10.1007/s11033-026-11815-w","DOIUrl":"https://doi.org/10.1007/s11033-026-11815-w","url":null,"abstract":"<p><p>The latest developments in DNA sequencing techniques have revealed genes that play a role in determining our vulnerability to diseases and have given us a deeper understanding of our genetic composition. A groundbreaking milestone in genetic engineering has transformed the capabilities of the scientific community in altering the genetic material of different organisms. Among recent innovations, the clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) has emerged as a powerful and precise tool for genome editing across diverse organisms. Its applications span immunotherapy, agriculture, poultry science, and human therapeutics, marking a transformative shift in biomedical and biotechnological research. However, the rapid progress and clinical translation of CRISPR/Cas9 have raised significant concerns regarding off-target effects, delivery challenges, long-term safety, and ethical implications. This review critically evaluates the CRISPR/Cas9 system by examining its molecular mechanism, editing efficiency, gene delivery approaches, and potential for inducing unintended mutations. A comparative analysis with other gene-editing tools is presented, emphasizing the advantages of CRISPR/Cas9 in programmability and editing efficiency. Furthermore, we discuss current advances including base editing, prime editing, and high-fidelity Cas variants, along with the ethical and societal dimensions of genome editing. This synthesis provides an updated perspective on the potential and limitations of CRISPR/Cas9 technology and highlights key areas for future research and responsible application.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in ophthalmology: innovations in diagnosis, therapy, and drug delivery.","authors":"Fatemeh Aziziyan, Mohammadreza Mahdipour, Behnaz Hadi, Shiva Sarani Asl, Hamed Afkhami, Mohsen Sheykhhasan","doi":"10.1007/s11033-026-11575-7","DOIUrl":"https://doi.org/10.1007/s11033-026-11575-7","url":null,"abstract":"<p><p>Most cells have the ability to secrete extracellular vesicles (EVs), which are nanoscale membrane-bound vesicles. EVs carry a diverse array of biomolecule, that play key roles in immunological modulation, intercellular communication, and the regulation of pathological and physiological processes. For EV-based diagnosis of ocular diseases, eye-derived biofluids serve as important sources. EVs found in these biofluids have emerged as promising biomarkers for the early detection of ocular diseases, as their molecular cargo can reflect the biology of their parent cells. Furthermore, due to their high biocompatibility and low immunogenicity, EVs have been explored as therapeutic agents and targeted drug delivery nanocarriers in various ocular diseases. In this review, we summarize the advancements in EV-based research focused on the detection and treatment of ocular diseases. We provide an overview of the origin of EV applications in ophthalmology, review techniques for isolating EVs from ocular biofluids, highlight EV bioengineering strategies for drug delivery, and present recent developments in EV-based diagnostics and therapeutics. Finally, we discuss ongoing clinical trials and conclude with an overview of the current challenges and future considerations for the clinical translation of EV-based approaches in ocular disease.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic modulation of pain pathways: toward a new era in pain therapy- a systematic review.","authors":"Sahar Jaffal, Ghada Jaffal","doi":"10.1007/s11033-026-11875-y","DOIUrl":"https://doi.org/10.1007/s11033-026-11875-y","url":null,"abstract":"<p><p>Gene therapy represents a new strategy in pain management targeting the causes of pain rather than its symptoms. This review summarizes recent advances across RNA interference (RNAi), viral vector delivery systems, CRISPR/Cas9, gene replacement therapy, and endogenous opioid gene delivery, emphasizing efficacy, safety, and mechanisms of action in pain conditions. RNAi and gene replacement techniques remain powerful tools for reducing pain and improving the quality of life by modulating pain-associated genes. Long-term relief may also be achieved with CRISPR/Cas9 and site-directed delivery using nanoparticle systems. Safety profiles especially with CRISPR/Cas9 remains a concern. A systematic search of Web of Science, Medline, Scopus, and Google Scholar identified 512 records (January 2010-March 2023). Following PRISMA screening, 18 studies met inclusion criteria. These studies evaluated strategies of gene therapy in neuropathy, arthritis, fibromyalgia, and complex regional pain syndrome. The review outlines available options and highlights preclinical findings.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA methylation in cardiovascular remodeling: Molecular mechanisms, biomarkers, and therapeutic strategies.","authors":"Huilin Li, Qiming Fan, Jiajun Sang, Chengxia Kan, Xiaodong Sun, Kexin Zhang","doi":"10.1007/s11033-026-11865-0","DOIUrl":"https://doi.org/10.1007/s11033-026-11865-0","url":null,"abstract":"<p><p>N⁶-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C) are dynamic and reversible RNA modifications that play important roles in cardiovascular diseases (CVDs). By regulating RNA stability, splicing, transport, translation, and degradation, m⁶A and m⁵C shape key pathological processes including endothelial dysfunction, inflammation, apoptosis, fibrosis, impaired contractility, and metabolic remodeling. Core regulators, including METTL3, METTL14, fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5), and YTH family proteins for m⁶A, as well as NSUN2, DNMT2, TET2, and ALYREF YBX1 for m⁵C related pathways, display disease stage specific and cell type-specific patterns across atherosclerosis, ischemic cardiomyopathy, heart failure, myocarditis, cardiomyopathy, and rheumatic heart disease, highlighting their potential as diagnostic and prognostic biomarkers. Therapeutically, pharmacological modulation of writers and erasers, adeno-associated virus-based gene delivery, and stem cell-based strategies show encouraging preclinical efficacy, while lifestyle interventions such as exercise may optimize the cardiac RNA methylation landscape. In addition, emerging RNA methylation marks, including N¹-methyladenosine (m¹A),7-methylguanosine (m⁷G), N⁶,2'-O-dimethyladenosine (m⁶Am), and oxidative cytosine derivatives such as 5-hydroxymethylcytosine (hm⁵C) and 5-formylcytosine (f⁵C), further expand the RNA modification landscape of cardiovascular remodeling by linking cap-dependent translation, mitochondrial protein synthesis, and stress adaptation. However, major challenges remain, including resolving RNA methylation dynamics at single-nucleotide and single-cell resolution, integrating RNA methylation with other regulatory layers, and achieving precise cardiac delivery with durable safety. With advances in multi-omics, spatial mapping, nanomedicine, and translational research, targeting RNA methylation offers a promising paradigm for improved diagnosis, risk stratification, and personalized therapy in cardiovascular disease.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-modal therapeutic approaches to inflammatory bowel disease: plant-derived compounds, nanoparticle drug delivery systems, and gene-based interventions.","authors":"Arooj Komal, Doua Ilyas, Muhammad Usman Khan, Muhammad Khalil Ur Rehman, Tayyaba Hassan, Hina Ayub, Nokhba Naqi, Noor Ullah, Umair Ilyas","doi":"10.1007/s11033-026-11888-7","DOIUrl":"https://doi.org/10.1007/s11033-026-11888-7","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder primarily affecting the gastrointestinal tract. The pathogenesis arises from complex interactions among genetic predisposition, immune dysregulation, and gut microbiota alterations. Recent advances in molecular biology, genomics, and microbiome research have identified novel therapeutic targets, enabling the development of innovative treatment strategies. Natural products derived from plants offer bioactive compounds with anti-inflammatory, antioxidant, and immunomodulatory properties, gaining attention for IBD symptom management. Conventional therapeutic management includes aminosalicylates, immunomodulators, corticosteroids, and biologics; however, 30-50% of patients show inadequate response, and oral drug delivery faces challenges due to gastrointestinal environmental heterogeneity. Recent years have witnessed substantial advances in nanoparticle-based drug delivery systems for IBD, offering improved targeting capabilities, enhanced therapeutic efficacy, and better tolerability through stimuli-responsive platforms (ROS-sensitive, pH-responsive) and active targeting strategies. Nanoparticle-mediated gene therapy, including siRNA, miRNA, and emerging CRISPR-based approaches, represents a paradigm-shifting strategy for modulating aberrant gene expression in IBD. This comprehensive review synthesizes the current understanding of IBD pathophysiology, evaluates both conventional and emerging therapeutic approaches, and provides critical analysis of advanced nanoparticle delivery systems and gene-based therapeutic strategies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparanase (HPSE) genetic variants as prognostic indicators in ovarian cancer: evidence from discovery and validation cohorts.","authors":"Inês Guerra de Melo, Valéria Tavares, Joana Savva-Bordalo, Mariana Rei, Joana Liz-Pimenta, Deolinda Pereira, Rui Medeiros","doi":"10.1007/s11033-026-11891-y","DOIUrl":"https://doi.org/10.1007/s11033-026-11891-y","url":null,"abstract":"<p><strong>Background: </strong>Heparanase uniquely cleaves heparan sulfate, the main component of the outer layer of endothelial cell plasma membranes, promoting tumour invasion and dissemination. However, it can also enhance tumour immune surveillance and clearance. heparanase's versatility extends to pro-thrombotic properties, such as the promotion of tissue factor release. Interestingly, elevated heparanase levels have been found in ovarian cancer (OC), which has a notably high incidence of venous thrombosis. Previously, single-nucleotide polymorphisms (SNPs) of HPSE were shown to modulate mRNA and protein levels, possibly predicting disease outcomes.</p><p><strong>Methods and results: </strong>Given the potential role of heparanase in OC, the implications of three SNPs - rs11099592, rs4364254 and rs4693608 - were investigated in OC patients. In the discovery cohort, rs11099592 TT genotype and rs4364254 C allele carriers showed lower survival time than their counterparts (log-rank test, p = 0.025 and p = 0.001, respectively). Validation cohort analysis confirmed the worse prognosis associated with the rs11099592 T allele and the rs4364254 C allele in non-serous (log-rank test, p = 0.016) and platinum-resistant (log-rank test, p = 0.044) OC patients, respectively. The rs4364254 C allele was associated with reduced HPSE expression in peripheral blood components (χ² test, p = 0.005), suggesting a protective role for HPSE in OC patients.</p><p><strong>Conclusions: </strong>HPSE rs11099592 and rs4364254 showed prognostic value, with T and C allele carriers, respectively, displaying worse clinical outcomes. These results indicate that heparanase could enable a tumour microenvironment shift towards a less aggressive cancer behaviour, facilitating leukocyte migration and anti-tumour responses. Further research should explore the dual mechanisms of this protein to improve OC management.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardamonin activates AMPK/FOXO3a/Nrf-2 axis to ameliorate oxidative stress in hyperlipidemia induced cardiac injury in mice.","authors":"Wenjia Yang, Qiuhong Jiao, Jiahong Chen, Longwu Xu, Haoyu Han, Junjie Feng, Xinyu Wang, Tao Wang, Chun Meng","doi":"10.1007/s11033-026-11895-8","DOIUrl":"https://doi.org/10.1007/s11033-026-11895-8","url":null,"abstract":"<p><strong>Background: </strong>Hyperlipidemia (HLP) is a prevalent metabolic disorder that induces myocardial injury through prolonged oxidative stress. Cardamonin (CAR), a natural chalcone from the Zingiberaceae family, is recognised for its antioxidant and anti-inflammatory activities; however, its specific role and underlying mechanisms in cardiovascular protection against HLP remain to be fully elucidated. This study aimed to investigate the protective effects of CAR on HLP-induced cardiac damage.</p><p><strong>Methods and results: </strong>An integrated approach combining network pharmacology and molecular docking was first employed to identify potential targets. Subsequently, in vivo experiments were conducted using C57BL/6J mice (n = 6 per group). HLP-induced cardiac injury models were established and treated with CAR. Network pharmacology and docking results revealed the AMP-activated protein kinase (AMPK)/forkhead box protein O3a (FOXO3a)/nuclear factor erythroid 2-related factor 2 (Nrf-2) signalling axis as a key target of CAR. The in vivo results demonstrated that CAR treatment significantly activated this pathway, thereby upregulating the expression of downstream antioxidant genes and alleviating oxidative stress. These molecular changes resulted in a significant reduction in myocardial histological damage and increased the expression of cardiac markers in HLP mice compared with those in the untreated group.</p><p><strong>Conclusions: </strong>CAR attenuates HLP-induced myocardial injury by activating the AMPK/FOXO3a/Nrf-2 axis to suppress oxidative stress. These findings provide new evidence for the therapeutic potential of CAR as a cardioprotective agent for managing hyperlipidemia-related complications.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-variant genotyping identifies association of TRPC6 rs36111323 with diabetic kidney disease in a South Indian population.","authors":"Ragulraja Sivakumar, J Shirly Angelin, Joy Wilson, S Srinivasan, J Akshaya Priya, S Bala Avinash, R Kathikeyan, A J Asirvatham, A Adlyne Reena, U Ramesh, Jayalakshmi Mariakuttikan","doi":"10.1007/s11033-026-11903-x","DOIUrl":"https://doi.org/10.1007/s11033-026-11903-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. Genetic factors contribute to inter-individual and population-specific susceptibility to DKD. Data from South Indian populations are limited, highlighting the need for region-specific genetic association studies in DKD.</p><p><strong>Methods and results: </strong>This case-control study included 125 South Indian individuals: 60 patients with diabetes and proteinuria (DKD), 34 patients with diabetes without kidney disease, and 31 healthy controls. Genomic DNA was isolated and nine variants were genotyped using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Variant frequencies were compared among groups. In-silico pathogenicity prediction tools and Odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analyses were used to assess the association between genetic variants and DKD risk. Data visualization was performed using R statistical software. Among the nine variants analyzed, the TRPC6 rs36111323 (G > A; p.A404V) was independently associated with DKD (OR = 2.76; 95% CI = 1.04-7.34; p = 0.0418). This variant was more frequent in patients with DKD compared with diabetic patients without nephropathy and healthy controls. Pathogenicity prediction analyses supported a potentially deleterious effect of the variant.</p><p><strong>Conclusions: </strong>The TRPC6 rs36111323 variant appears to be associated with increased susceptibility to diabetic kidney disease in a South Indian population, suggesting a population-specific genetic risk factor. Validation in larger cohorts and functional studies is warranted to clarify its role and potential application in precision nephrology.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic MAGEA4 directs neuroendocrine differentiation and survival in prostate cancer cells through the SIRT1/Acetyl-p53/BCL-2 axis.","authors":"Maresha Ramakrishna, Teja Nallavolu, Ramesh Ummanni","doi":"10.1007/s11033-026-11878-9","DOIUrl":"https://doi.org/10.1007/s11033-026-11878-9","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine prostate cancer (NEPC) is a highly aggressive and therapy-resistant subtype of prostate cancer (PCa) that emerges following the androgen receptor (AR) targeted therapies. Identification of potential molecular drivers governing neuroendocrine differentiation (NED) and survival is critical for developing therapeutic strategies. Cancer-testis antigens of the Melanoma-associated antigen family (MAGE) are the emerging players of oncogenic regulators. However, their role in NEPC remains unexplored.</p><p><strong>Methods: </strong>Proteomic and transcriptomic analyses were performed to identify differential expression of target proteins in NEPC. Functional characterization of MAGEA4 was performed using stable overexpression, siRNA-mediated knockdown in androgen-dependent/independent, and NEPC cell lines. For target validation, neuroendocrine markers, morphological characteristics, apoptotic signaling, oxidative pathways, and cell survival were evaluated using molecular, biochemical, and pharmacological approaches targeting SIRT1, p53 acetylation, BCL-2/BCL-XL and NRF2.</p><p><strong>Results: </strong>MAGEA4 was upregulated in NEPC cells and in advanced prostate cancer tissues. Overexpression of MAGEA4 induced neuroendocrine differentiation, promoted androgen-independent survival, and conferred resistance to apoptosis. Furthermore, MAGEA4 upregulated SIRT1 activity, which deacetylated p53, thereby suppressing pro-apoptotic signaling. Additionally, MAGEA4 enhanced the oxidative stress resistance through activation of the SIRT1/PGC-1α/NRF2 axis, suggesting a role in retaining the NED phenotype. In MAGEA4-positive cells, inhibition of BCL-2 and/or NRF2 attenuated the neuroendocrine characteristics, suggesting therapeutic vulnerability.</p><p><strong>Conclusion: </strong>These findings highlight that MAGEA4 may contribute to neuroendocrine differentiation and survival in prostate cancer cells, and may represent a potential therapeutic vulnerability in aggressive prostate cancers.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational construction of rpsL or/and rpoB merodiploids affects biosynthesis of secondary metabolite in Streptomyces.","authors":"Chen Lu, Xiaoyu Pan, Shiying Yang, Jinyao Zhang, Yujie Jiang, Yongyong Zhang, Andreas Bechthold, Zheng Ma","doi":"10.1007/s11033-026-11871-2","DOIUrl":"https://doi.org/10.1007/s11033-026-11871-2","url":null,"abstract":"<p><strong>Background: </strong>Ribosome engineering technology typically involves resistance screening of streptomycin and rifampin to introduce point mutations in genes ribosomal protein S12 (rpsL) or RNA polymerase (rpoB), thereby enhancing the synthesis level of secondary metabolites in Streptomyces. Currently, directly introducing copies of genes rpsL and rpoB carrying \"beneficial mutations\" to construct diploids has become a more rapid and efficient method for obtaining high-yielding Streptomyces strains.</p><p><strong>Methods and results: </strong>We directly introduced these beneficial mutations (rpsL: K88E/P91S; rpoB: S433L/H437Y/R440C) to construct single or combined merodiploids. Introducing rpsL-K88E promoted secondary metabolite biosynthesis in both strains S. coelicolor M145 and S. diastatochromogenes 1628, notably increasing tetramycin A production by 66% in 1628-rpsL-K88E. However, rpsL-P91S yielded no significant positive effects. Regarding rpoB, the M145-rpoB-H437Y strain showed a modest enhancement, with actinorhodin and undecylprodigiosin yields increasing by 20% and 22%. In S. diastatochromogenes 1628, introducing rpoB-H437Y, rpoB-R440C and rpoB-S433L promoted the synthesis of toyocamycin and tetraene macrolides to varying degrees.</p><p><strong>Conclusions: </strong>Constructing a diploid by directly introducing the rpsL and rpoB genes carrying \"beneficial mutations\" is an effective strategy to enhance the synthesis level of secondary metabolites, whether for the model strain S. coelicolor M145 or the industrial strain S. diastatochromogenes 1628.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"53 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}