ACS Synthetic Biology最新文献_第3页

Enhanced d-Pantothenic Acid Biosynthesis in Corynebacterium glutamicum by the CPSPC System and Spatial Organization Strategy CPSPC系统与空间组织策略对谷氨酸棒状杆菌d-泛酸生物合成的促进作用

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-23 DOI: 10.1021/acssynbio.6c00280

Qing Yang, Bo Zhang, Lianggang Huang, Junping Zhou, Cuicui Liu, Zhiqiang Liu, Yuguo Zheng

{"title":"Enhanced d-Pantothenic Acid Biosynthesis in Corynebacterium glutamicum by the CPSPC System and Spatial Organization Strategy","authors":"Qing Yang, Bo Zhang, Lianggang Huang, Junping Zhou, Cuicui Liu, Zhiqiang Liu, Yuguo Zheng","doi":"10.1021/acssynbio.6c00280","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00280","url":null,"abstract":"d-Pantothenic acid (D-PA) is an essential precursor of coenzyme A and the acyl carrier protein. Its biosynthesis requires abundant precursors and precise regulation of the multifunctional enzyme, ketopantoate reductase. Here, we engineered Corynebacterium glutamicum for enhanced D-PA production through metabolic engineering, spatial enzyme organization, and a dynamically controlled CPSPC system (Coenzyme and Product Synthesis Pathway Coupling System). Competing pathways were suppressed, while target synthesis routes and 5,10-methylenetetrahydrofolate supply were strengthened. A RIAD-RIDD-mediated substrate channel between dihydroxy acid dehydratase and ketopantoate hydroxymethyltransferase was used to optimize enzymatic stoichiometry and localization. After functionalizing a glycine riboswitch in C. glutamicum, we developed the CPSPC system that dynamically couples one-carbon metabolism with D-PA synthesis. Fluorescence tracking confirmed its glycine-responsive regulation. The engineered strain DPAj-2-tuf achieved 23.06 g/L in a 5 L bioreactor over 63 h, productivity of 0.37 g/L/h, and glucose yield of 0.17 g/g. These outcomes offer an efficient and scalable strategy for industrial D-PA production using C. glutamicum.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4060–4074"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interpretable Protein−Nucleic Acid Binding Site Prediction via Domain-Guided Multimodal Learning 可解释的蛋白质-核酸结合位点预测通过域引导的多模式学习

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-10-05 DOI: 10.1021/acssynbio.6c00340

Wenyu Xi, Ruheng Wang, Xiucai Ye, Tetsuya Sakurai, Leyi Wei

{"title":"Interpretable Protein−Nucleic Acid Binding Site Prediction via Domain-Guided Multimodal Learning","authors":"Wenyu Xi, Ruheng Wang, Xiucai Ye, Tetsuya Sakurai, Leyi Wei","doi":"10.1021/acssynbio.6c00340","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00340","url":null,"abstract":"Accurate identification of protein−nucleic acid binding sites is essential for elucidating molecular mechanisms and for enabling structure-based drug discovery. Existing computational approaches struggle to jointly model sequence, structure, and domain knowledge, which limits both predictive accuracy and interpretability. We present BiMTBind, a domain-guided multimodal deep learning framework that integrates bidirectional state-space modeling with Transformer-based attention for residue-level binding site prediction. The model explicitly incorporates protein-domain annotations as biological priors to guide attention toward functionally relevant regions. Multi-source featurescontextual embeddings from protein language models and handcrafted structural descriptorsare fused via a learnable gating mechanism that adaptively weights each modality. This design enables the model to capture both global dependencies and local context. Extensive evaluations across diverse DNA and RNA benchmarks show that BiMTBind consistently outperforms state-of-the-art sequence- and structure-based methods on multiple metrics, including F1, MCC, and AUC. Case studies further show that domain-guided attention improves interpretability by aligning predicted binding residues with annotated functional domains. These results highlight the effectiveness of combining biologically informed priors with deep multimodal representation learning, offering a scalable and generalizable approach for protein−nucleic acid binding site prediction.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4132–4144"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolutionary Rewiring of Sugar Transporter Gene manXYZ Enables Highly Coordinated Non-glucose Metabolisms in Engineered Lactic Acid Bacterium 糖转运基因manXYZ的进化重组使工程乳酸菌的非糖代谢高度协调

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-23 DOI: 10.1021/acssynbio.6c00477

Jiao Liu, Niling He, Yi Zhang, Bin Zhang, Jie Bao

{"title":"Evolutionary Rewiring of Sugar Transporter Gene manXYZ Enables Highly Coordinated Non-glucose Metabolisms in Engineered Lactic Acid Bacterium","authors":"Jiao Liu, Niling He, Yi Zhang, Bin Zhang, Jie Bao","doi":"10.1021/acssynbio.6c00477","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00477","url":null,"abstract":"Achieving highly coordinated metabolism and efficient conversion of lignocellulose-derived non-glucose sugars remains a major challenge for biorefinery microbial cell factories. Herein, we report an evolutionary rewiring of an engineered lactic acid bacterium Pediococcus acidilactici G1 with enhanced co-utilization of glucose, xylose, arabinose, mannose, and galactose for l-lactic acid generation. Transcriptomic analysis revealed the extraordinary upregulation of a unique sugar transporter gene cluster, manXYZ, while genome re-sequencing identified two convergent mutations in the transcriptional regulators CcpA (T65I) and LevR (E159G). Back mutation, reverse metabolic engineering, and electrophoretic mobility shift assays (EMSA) were then employed to investigate the regulation of manXYZ expression by CcpA T65I and LevR E159G. Collectively, our findings demonstrate that recurrent mutations in transcriptional regulators CcpA and LevR drove the significant upregulation of the manXYZ sugar transporter cluster during adaptive evolution, highlighting the importance of sugar transport in improving non-glucose sugar metabolism. This study not only develops a promising strain for practical biorefinery applications but also provides a new sugar transporter solution, rather than regular intracellular metabolic pathway engineering, for highly efficient non-glucose sugars utilization in P. acidilactici.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4252–4265"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Mammalian Surface Display Platform to Optimize the Antigenicity of Viral Proteins 优化病毒蛋白抗原性的哺乳动物表面展示平台

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-10-07 DOI: 10.1021/acssynbio.6c00027

Jayani Christopher, Caitlin Harris, Daniel J. Marston, Brianna Rhodes, McKenzie Frazier, Mihai L. Azoitei

{"title":"A Mammalian Surface Display Platform to Optimize the Antigenicity of Viral Proteins","authors":"Jayani Christopher, Caitlin Harris, Daniel J. Marston, Brianna Rhodes, McKenzie Frazier, Mihai L. Azoitei","doi":"10.1021/acssynbio.6c00027","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00027","url":null,"abstract":"Vaccine development often involves modifying native viral proteins to enhance their stability and antigenicity, as seen in approved Covid-19 vaccines and multiple HIV vaccine candidates currently under investigation. High throughput screening on the surface of mammalian cells enables the rapid evaluation of oligomeric, glycosylated viral proteins and the identification of mutations that improve their properties for vaccine design. Here, we developed an experimental platform that uses the PiggyBac transposon system to display libraries of viral protein variants on the surface of mammalian cells for efficient screening. This approach addresses common challenges in existing mammalian display systems, including low transfection efficiency and the need to develop stable cell lines for iterative selection rounds. The new platform was validated by displaying diverse viral proteins and screening influenza hemagglutinin libraries to identify mutations that increased binding of broadly cross-reactive antibodies to a conserved but partially occluded epitope of interest for the development of a universal influenza vaccine. These results demonstrate the potential of this mammalian display platform to rapidly engineer immunogens with desired antigenic properties for vaccine design.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"3993–4006"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149211013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Promoter Engineering in Yeast Cell Factories: Strategies, Applications, and Perspectives 酵母细胞工厂启动子工程：策略、应用和展望

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-25 DOI: 10.1021/acssynbio.6c00207

Zhenzhen Bai, Tian Jiao, Farshad Darvishi, Haodong Chu, Zheng Wang, Shuobo Shi

{"title":"Promoter Engineering in Yeast Cell Factories: Strategies, Applications, and Perspectives","authors":"Zhenzhen Bai, Tian Jiao, Farshad Darvishi, Haodong Chu, Zheng Wang, Shuobo Shi","doi":"10.1021/acssynbio.6c00207","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00207","url":null,"abstract":"Yeasts serve as premier eukaryotic hosts for microbial cell factories, enabling the production of recombinant proteins, biofuels, and high-value natural products. Precise transcriptional control is paramount for balancing complex metabolic pathways and maximizing target product yields. Promoters, as the key regulatory elements governing transcription initiation, have thus become a focal point of metabolic and synthetic biology engineering. This review surveys promoter architecture, function, and engineering in yeast. It outlines promoter structure, from core elements to upstream regulatory sequences, and reviews current and emerging strategies for discovery, optimization, and de novo design, including random mutagenesis, combinatorial assembly, rational design based on transcription factor binding sites, intron-mediated enhancement, cross-species approaches. Importantly, this review highlights the rapidly growing role of machine learning (ML) and artificial intelligence (AI) in promoter engineering, from predictive modeling of promoter strength to in silico generation of synthetic variants. Special emphasis is placed on synthetic promoter engineering to yield tunable and inducible toolkits. The review also highlights applications in yeast cell factories, such as metabolic pathway optimization, dynamic regulation, high-throughput strain screening, and recombinant protein production. By summarizing these recent advances, it serves as a practical resource for researchers aiming to achieve precise metabolic control and improve bioproduction outcomes in yeast.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"3891–3910"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149211018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic Engineering of the Thermophilic Fungus Myceliophthora thermophila for l-glutamate Production from Lignocellulosic Biomass 嗜热真菌嗜热霉菌从木质纤维素生物质中生产l-谷氨酸的代谢工程

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-29 DOI: 10.1021/acssynbio.6c00533

Defei Liu, Yutong Ge, Jingen Li, Chaoguang Tian

{"title":"Metabolic Engineering of the Thermophilic Fungus Myceliophthora thermophila for l-glutamate Production from Lignocellulosic Biomass","authors":"Defei Liu, Yutong Ge, Jingen Li, Chaoguang Tian","doi":"10.1021/acssynbio.6c00533","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00533","url":null,"abstract":"l-Glutamic acid is conventionally produced by bacteria from starch-derived sugar, while its production in eukaryotic hosts remains rarely reported. The thermophilic ascomycete fungus Myceliophthora thermophila has been developed as a platform for producing value-added chemicals from lignocellulosic biomass. In this study, we explored the feasibility of engineering M. thermophila for l-glutamate production from biomass-derived carbon sources. Genome-scale metabolic modeling indicated that M. thermophila has the stoichiometric capacity to synthesize l-glutamate from glucose and ammonia. Experimental fermentation confirmed extracellular l-glutamate accumulation, and medium optimization revealed that nitrogen source selection and extracellular pH homeostasis strongly affected l-glutamate accumulation. Overexpression of the native NADPH-dependent glutamate dehydrogenase gene gdh1 markedly increased glutamate production. Additional engineering strategies targeting membrane-associated metabolism, glutamate transport, mitochondrial precursor transport, and competing α-ketoglutarate-consuming pathways provided insights into the regulation of glutamate metabolism in filamentous fungi. The engineered strain produced 3.41 g/L l-glutamate from glucose. Moreover, 1.50 g/L and 1.49 g/L l-glutamate were obtained directly from cellulose and raw corncob, respectively. This study establishes M. thermophila as a proof-of-concept thermophilic fungal platform for l-glutamate production from lignocellulosic carbon sources and provides a framework for engineering amino acid biosynthesis in cellulolytic fungi.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4327–4336"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Redirecting Carbon Flux Toward 2-Ketoglutarate Enables Photoautotrophic 1,4-Butanediol Production from CO2 将碳通量重定向到2-酮戊二酸盐使CO2光自养1,4-丁二醇生产成为可能

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-23 DOI: 10.1021/acssynbio.6c00541

Alex McGill, Xong Vue, Tanner R. Treece, Jake N. Gonzales, Shota Atsumi

{"title":"Redirecting Carbon Flux Toward 2-Ketoglutarate Enables Photoautotrophic 1,4-Butanediol Production from CO2","authors":"Alex McGill, Xong Vue, Tanner R. Treece, Jake N. Gonzales, Shota Atsumi","doi":"10.1021/acssynbio.6c00541","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00541","url":null,"abstract":"Engineered cyanobacteria offer a sustainable platform for the conversion of light and CO2 into value-added chemicals. Unlike heterotrophic systems, cyanobacteria do not require organic carbon sources such as glycerol, glucose, or sucrose. In this study, we engineered Synechococcus elongatus PCC 7942 (hereafter 7942) for the production of 1,4-butanediol (14BDO), a precursor used in the synthesis of pharmaceuticals, biodegradable polymers, and resins, directly from CO2. To identify a suitable biosynthetic route, we evaluated three heterologous 14BDO pathways previously developed in heterotrophic hosts. Among these, the carboxylic acid reductase (Car) pathway supported 14BDO production directly from CO2 without supplementation of an exogenous carbon source, whereas the Weimberg pathway required d-xylose supplementation and the CoA-dependent pathway did not produce detectable 14BDO. We therefore focused on the Car pathway and improved production by rewiring carbon flux through the incomplete tricarboxylic acid pathway, directing intermediates toward 2-ketoglutarate as a key metabolic node. Further engineering, including additional expression of ppc and gltA and deletion of glgC, increased 14BDO production, consistent with enhanced carbon availability for 14BDO biosynthesis. This work establishes a functional route for photoautotrophic 14BDO production from CO2 and demonstrates the importance of carbon flux engineering for improving production of non-native chemicals in cyanobacteria.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4337–4344"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-Throughput Promoter Engineering of Vacuolar-Associated Genes Enhances Extracellular Betanin Accumulation in Yarrowia lipolytica 液泡相关基因的高通量启动子工程促进脂性耶氏菌胞外β素积累

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-10-02 DOI: 10.1021/acssynbio.6c00324

Shengbao Wang, Tommaso Fumagalli, Sivachandiran Somasundaram, Muyi Song, David Lokjær Faurdal, Wei Jiang, Irina Borodina

{"title":"High-Throughput Promoter Engineering of Vacuolar-Associated Genes Enhances Extracellular Betanin Accumulation in Yarrowia lipolytica","authors":"Shengbao Wang, Tommaso Fumagalli, Sivachandiran Somasundaram, Muyi Song, David Lokjær Faurdal, Wei Jiang, Irina Borodina","doi":"10.1021/acssynbio.6c00324","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00324","url":null,"abstract":"Betanin is a natural red pigment that accumulates within plant vacuoles. It is hypothesized that vacuolar sequestration could also restrict the extracellular accumulation of heterologously produced betanin in the yeast Yarrowia lipolytica. To investigate the role of vacuolar functions in influencing extracellular betanin levels, we employed the TUNEYALI platform to generate a promoter-engineering library targeting 21 vacuole-associated genes. Screening 470 transformants identified nine variants with enhanced extracellular betanin accumulation. Whole-genome sequencing revealed that all nine isolates harbored disruptions in YALI1_C31684g, the gene most closely related to Saccharomyces cerevisiaeVPS8, which encodes a CORVET-specific tethering subunit. Reverse engineering confirmed that partial knockdown of YALI1_C31684g led to a 1.18-fold increase in total betanin production and a 61.7% increase in extracellular betanin levels, whereas complete deletion of the gene reduced extracellular accumulation. Quantitative PCR analysis showed that the promoter knockout construct maintained approximately 47% of wild-type transcript levels, suggesting that a partial loss of function is more effective than a complete loss of function in enhancing extracellular betanin. Confocal microscopy demonstrated extensive vacuolar fragmentation in the knockdown strain, with the highest levels of extracellular betanin correlating with the most pronounced fragmentation phenotype. Collectively, these findings identify YALI1_C31684g as a key regulator of extracellular betanin accumulation in Y. lipolytica and demonstrate that modulating vacuolar trafficking functions can enhance the extracellular fraction of metabolites stored in vacuoles.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4124–4131"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient Production of Vanillyl Alcohol in Escherichia coli via Protein and Pathway Engineering 利用蛋白质和途径工程在大肠杆菌中高效生产香草醇

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-23 DOI: 10.1021/acssynbio.6c00309

Jinyi Li, Yong Du, Jia Wang, Xiaolin Shen, Hao Liang, Xinxiao Sun, Qipeng Yuan

{"title":"Efficient Production of Vanillyl Alcohol in Escherichia coli via Protein and Pathway Engineering","authors":"Jinyi Li, Yong Du, Jia Wang, Xiaolin Shen, Hao Liang, Xinxiao Sun, Qipeng Yuan","doi":"10.1021/acssynbio.6c00309","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00309","url":null,"abstract":"Vanillyl alcohol (VNA) is a high-value compound used in the pharmaceutical industry and other fields. Its microbial de novo biosynthesis is severely limited by the low catalytic efficiency of O-methyltransferase. Here, we constructed a V314I mutant of caffeate O-methyltransferase via structure-guided protein engineering, which showed a 95% increase in catalytic efficiency toward 3,4-dihydroxybenzyl alcohol in Escherichia coli. Molecular simulations revealed that the mutation narrows the active-site cavity, constraining the smaller substrate into a catalytically competent orientation. To alleviate growth inhibition caused by 3,4-dihydroxybenzaldehyde accumulation, alcohol dehydrogenase gene ADH6 was introduced into the host. Moreover, S-Adenosylmethionine supply was enhanced by genomic integration of luxS-mtn and methionine supplementation. Finally, a VNA titer of 6.21 g/L was achieved in a 3 L fermenter from glycerol. This work establishes a VNA biomanufacturing platform and demonstrates an integrative strategy for the microbial production of methylated aromatic natural products, combining enzyme active-site spatial engineering and pathway engineering.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"4112–4123"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating Synthetic Biology, Systems Biology, and Bioprocessing to Advance Terpene Production in Cyanobacteria 整合合成生物学、系统生物学和生物处理，促进蓝藻中萜烯的生产

IF 4.5 2区生物学

ACS Synthetic Biology Pub Date : 2026-10-16 Epub Date: 2026-09-25 DOI: 10.1021/acssynbio.6c00175

Tinggeng Lai, Esther O. Amosu, Joseph Raphael, Tim McCubbin, Esteban Marcellin, Ian T. Paulsen, Alescia Cullen

{"title":"Integrating Synthetic Biology, Systems Biology, and Bioprocessing to Advance Terpene Production in Cyanobacteria","authors":"Tinggeng Lai, Esther O. Amosu, Joseph Raphael, Tim McCubbin, Esteban Marcellin, Ian T. Paulsen, Alescia Cullen","doi":"10.1021/acssynbio.6c00175","DOIUrl":"https://doi.org/10.1021/acssynbio.6c00175","url":null,"abstract":"Cyanobacteria act as efficient “solar-powered” cell factories, converting CO2 and light into valuable products while thriving in seawater or wastewater. Cyanobacteria are attractive hosts for terpenoid bioproduction because they natively produce terpene precursors. Our review found that while cyanobacteria have been engineered to produce 26 different terpenoids, only 1 of the 63 terpene bioproduction studies achieved titers in the g/L range. To identify the path forward towards maximizing cyanobacterial terpene titers and productivity, this review has taken a twofold approach. First, it synthesizes progress and bottlenecks across three interconnected dimensions: synthetic biology, systems biology, and bioprocess engineering. Second, it addresses a limitation of the field by harmonizing all cyanobacterial terpenoid bioproduction titers into consistent units for the first time, enabling like-for-like comparisons. Through this, three factors were found consistent across the top five highest titers: terpene precursor overexpression, fermentation optimization (using nutrient-rich media and/or a bioreactor), and the production of a volatile terpenoid. On the other hand, while systems biology-informed metabolic engineering can significantly increase cellular health and productivity, it is the least utilized strategy. Taken together, this review highlights the importance of multifaceted approaches to improving cyanobacterial terpene production.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"15 10","pages":"3872–3890"},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0