ACS Synthetic Biology最新文献

{"title":"Engineered Gram-Positive Based Quorum Sensing for Metabolic Control in Escherichia coli","authors":"Michael J. Ream,&nbsp; and ,&nbsp;Kristala L. J. Prather*,&nbsp;","doi":"10.1021/acssynbio.5c00433","DOIUrl":"10.1021/acssynbio.5c00433","url":null,"abstract":"<p >Quorum sensing (QS) is a cell-to-cell communication system that allows microbial communities to collaborate and function as a collective. QS functions as a population-dependent regulator by producing signals that scale with cell concentration, allowing surrounding cells to recognize the signal and activate the associated genes at a certain population density. Though many regulatory systems have been characterized, much of the engineering focus has been on a small subset of the expansive QS circuits that exist within nature. To expand the available QS circuits for use in <i>Escherichia coli</i>, two Gram-positive systems were identified as useful candidates: the Agr system, from the therapeutically relevant <i>Staphylococcus aureus</i>, and the Com system, from the model Gram-positive organism <i>Bacillus subtilis</i>. These QS systems were implemented and improved for functionality by modifying the expression strength of circuit components. Each system displayed tight control of their cognate promoters with the Com system reaching a final dynamic range of 2.27 ± 0.05, while the Agr system was improved to a dynamic range of 4.05 ± 0.43. The Agr system was then applied to downregulate endogenous genes <i>tyrA</i>, <i>pheA</i>, <i>trpE</i>, <i>ppc</i>, and <i>pabB</i> via CRISPRi. This regulation strategy allowed for the production of salicylic acid in <i>E. coli</i> MG1655 by diverting metabolic flux toward the target pathway, demonstrating the utility of Agr as a tightly regulated control system in <i>E. coli</i>.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 9","pages":"3734–3743"},"PeriodicalIF":3.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815268","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}

{"title":"Characterizing and Engineering a Succinate-Responsive Biosensor System in Escherichia coli","authors":"Yusong Zou,&nbsp;Yuanxin Qian,&nbsp;Connor Parish,&nbsp;Logan Huddle and Yajun Yan*,&nbsp;","doi":"10.1021/acssynbio.5c00290","DOIUrl":"10.1021/acssynbio.5c00290","url":null,"abstract":"<p >Metabolic engineering enables the sustainable production of valuable compounds, but challenges such as metabolic imbalances and limited regulatory tools hinder optimal yields and efficiencies. Transcription factor (TF)-based biosensors have emerged as robust solutions, allowing dynamic sensing and regulation of intracellular metabolites. However, their limited diversity often restricts their broader applications in metabolic engineering. To overcome this limitation, it is essential to develop biosensors that are responsive to central metabolic intermediates, enabling more versatile pathway control. In this study, we characterized a succinate-responsive biosensor system regulated by the IclR family TF, PcaR, and elucidated the dual-function mechanism observed in this PcaR biosensor system. Initially, we fine-tuned the expression of PcaR, fully recovering the corresponding promoter strength. Then, we discovered a dual-function mechanism of PcaR through homologue pairing, further elucidated by employing site-directed mutagenesis and promoter engineering. Meanwhile, we established a succinate-responsive biosensor library guided by PcaR–succinate complex analysis with varied dynamic ranges, identifying the superior P1-AII variant with nearly a 33-fold improvement in dynamic range. Finally, we constructed a bifunctional regulatory circuit controlled by succinate and a single regulator, demonstrating its potential for dynamic metabolic regulation. Given the primary role of succinate in central metabolism, the engineered PcaR biosensor system provides a promising tool for real-time metabolic monitoring and optimization of microbial production.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 9","pages":"3510–3519"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the Transformation Efficiency of Synechococcus sp. PCC 7002 via Methylome-Guided Premethylation of DNA","authors":"Andrew Hren,&nbsp;William G. Alexander,&nbsp;Joshua P. Abraham,&nbsp;Melissa P. Tumen-Velasquez,&nbsp;Michael Melesse Vergara,&nbsp;Adam M. Guss,&nbsp;Brian F. Pfleger*,&nbsp;Jerome M. Fox* and Carrie A. Eckert*,&nbsp;","doi":"10.1021/acssynbio.5c00370","DOIUrl":"10.1021/acssynbio.5c00370","url":null,"abstract":"<p >Cyanobacteria are promising microbial platforms for a diverse set of biotechnology applications, from living materials to photosynthetic chemical production, but are less well characterized than commonly engineered microbes such as <i>Escherichia coli</i>. This study facilitates genetic engineering in <i>Synechococcus</i> sp. PCC 7002, a fast-growing, halotolerant, and naturally competent strain, by identifying ten native methylation motifs and designing shuttle strains that mimic the native methylation state by expressing a subset of heterologous methyltransferases. DNA methylation in <i>E. coli</i> with as few as two active methyltransferases increased transformation efficiency up to 30-fold across four distinct integration sites in PCC 7002. This work provides an experimental framework to bypass native restriction-modification systems for efficient genome editing and metabolic engineering in nonmodel bacteria.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3258–3264"},"PeriodicalIF":3.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioluminescence-Driven Optimization of Geminivirus-Based Vectors as Tools for Plant Biotechnology","authors":"Elena Garcia-Perez,&nbsp;Victor Vazquez-Vilriales,&nbsp;Marta Vazquez-Vilar,&nbsp;Araceli G. Castillo,&nbsp;Karen S. Sarkisyan,&nbsp;Rosa Lozano-Duran,&nbsp;Eduardo R. Bejarano and Diego Orzaez*,&nbsp;","doi":"10.1021/acssynbio.5c00164","DOIUrl":"10.1021/acssynbio.5c00164","url":null,"abstract":"<p >Viral replicons are valuable tools in plant biotechnology, widely utilized to increase recombinant protein production. Their ability to amplify gene dosage in a trigger-dependent manner also opens doors to regulatory applications. This work focuses on optimizing geminivirus-based vectors for Synthetic Biology applications in plants, using autobioluminescence as a sensitive, real-time reporter to characterize gene expression. Specifically, geminivirus-based synthetic replicons derived from bean yellow dwarf virus (BeYDV), tomato yellow leaf curl virus (TYLCV), and beet curly top virus (BCTV) were engineered and assessed for basal expression, inducibility, and recombinant protein coexpression potential. Our study provided insights into the strengths and limitations of each geminiviral replicon. BeYDV replicon displayed a robust activation profile suitable for complex tasks such as multigene expression, while TYLCV showed high expression levels despite moderate basal leakage. In contrast, BCTV demonstrated less favorable control and expression levels. Through a bioluminescence-based screening, the TYLCV system was further optimized to improve regulatory precision. These findings highlight the versatility of geminivirus replicons, paving the way for future engineering of synthetic gene circuits in plants.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3078–3090"},"PeriodicalIF":3.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Pot Detection of Biomarker Apurinic/Apyrimidinic Endonuclease 1 Based on the Modified-crRNA Regulated Trans-Cleavage Activity of CRISPR/Cas12a","authors":"Sheng Ding*,&nbsp;Haiyan Li,&nbsp;Jing Li,&nbsp;Dianxiang Lu*,&nbsp;Jin Yang* and Zhuo Tang,&nbsp;","doi":"10.1021/acssynbio.5c00335","DOIUrl":"10.1021/acssynbio.5c00335","url":null,"abstract":"<p >Apurinic/apyrimidinic endonuclease 1 (APE1), a critical protein in DNA repair, plays indispensable roles in the maintenance of cellular homeostasis, thereby garnering significant attention as a biomarker and therapeutic target for various disorders. Current APE1 sensing methods always require multiple enzymes or complex signal amplification. The high programmability of the CRISPR/Cas12-based signal amplifier provides a new chance for developing biosensors. In this study, we introduce a novel method for the detection of APE1 by leveraging the discovery that modulating the length of modified DNA within CRISPR RNA (crRNA) enables precise control over the trans-cleavage activity of CRISPR/Cas12a. By designing a specific crRNA, the APE1-mediated activity recovery of Cas12a (ARC) was developed for rapid, specific, and one-pot detection of APE1. ARC presented a detection limit of 1.74 × 10^–6 U/μL with high specificity in detecting APE1 in biological samples. Besides, this simple method was feasible for APE1 inhibition assays, highlighting its potential for inhibitor screening and evaluation. Collectively, our findings present an innovative approach for APE1 activity analysis and expand the CRISPR-based non-nucleic acid target sensing toolbox through a novel crRNA design.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3186–3195"},"PeriodicalIF":3.9,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768147","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}

{"title":"Combinatorial Tuning of 5′UTR and N-Terminal Coding Sequences for Enhanced Recombinant Protein Expression in Corynebacterium glutamicum","authors":"Xiuxia Liu,&nbsp;Guangying Li,&nbsp;Sinan Cui,&nbsp;Yankun Yang*,&nbsp;Chun li Liu and Zhonghu Bai,&nbsp;","doi":"10.1021/acssynbio.5c00250","DOIUrl":"10.1021/acssynbio.5c00250","url":null,"abstract":"<p >The 5′UTR sequence and N-terminal coding sequence (NCS) have been used to regulate gene expression in <i>Corynebacterium glutamicum</i> (<i>C. glutamicum</i>) microbial cell factories. However, there is currently insufficient research on the relationship between these expression element sequences and the protein expression rate in <i>C. glutamicum</i>. This study established a pattern between 5′UTR and NCS feature sequences and protein expression and validated their effects on protein expression. First, a 5′UTR library and a NCS library containing base N were constructed separately, and a continuous regulatory range across 5 orders of magnitude for the enhanced green fluorescent protein (eGFP) expression was achieved in both libraries by fluorescence activated cell sorting (FACS) and high-throughput sequencing. Next, the relationship between sequence information and protein expression was established based on the 5′UTR sequence and NCS sequence characteristics analysis in terms of CG content, minimum free energy (MFE), tRNA adaptability index, and deep learning. Moreover, four 5′UTR characteristic sequences and four NCS characteristic sequences were finally screened, which showed strong compatibility with different exogenous proteins. Furthermore, dynamic adjustment of eGFP fluorescence intensity from 45% to 511% was achieved through 16 different combinations of the screened four 5′UTR and four NCS sequences, confirming the synergistic effect of these two components. At the same time, these combinations also have a wide range of dynamic regulation of protein expression levels of other recombinant proteins such as mCherry and heavy chain antibody. This study provided a potential tool for finely regulating gene expression or protein production in <i>C. glutamicum</i>.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3105–3115"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764216","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}

{"title":"Recombinase-Mediated Cassette Exchange-Based CRISPR Activation Screening Identifies Hyperosmotic Stress-Resistant Genes in Chinese Hamster Ovary Cells","authors":"Minhye Baek,&nbsp;Seokchan Kweon,&nbsp;Yujin Kim,&nbsp;Nathan E. Lewis,&nbsp;Jae Seong Lee and Gyun Min Lee*,&nbsp;","doi":"10.1021/acssynbio.5c00268","DOIUrl":"10.1021/acssynbio.5c00268","url":null,"abstract":"<p >Chinese hamster ovary (CHO) cells are ubiquitously used for therapeutic protein production. However, fed-batch culture, typically used for large-scale production, often induces hyperosmotic stress, negatively impacting cell growth and productivity. To identify genes conferring resistance to hyperosmotic stress, we performed genome-wide CRISPRa screening in bispecific antibody (bsAb)-producing CHO (CHO-bsAb) cells. Using a virus-free recombinase-mediated cassette exchange (RMCE) system, we established a CRISPRa library and cultured cells in standard and hyperosmolar media. Next-generation sequencing identified 122 significantly enriched and 171 significantly depleted genes under hyperosmolar conditions, with functional enrichment analysis highlighting pathways related to cell proliferation and transcriptional regulation. Among the enriched genes, CRISPRa-based activation of 24 candidates demonstrated that 23 improved cell growth under hyperosmolar conditions. Notably, stable expression of <i>Siah2</i> or <i>C2cd4a</i> significantly enhanced cell growth, and optimizing their expression levels increased bsAb production by up to 1.3-fold. Additional knockout of <i>Zfr</i>, previously identified in CRISPR knockout screening, further improved cell growth and bsAb production, demonstrating the synergistic benefits of integrating CRISPR knockout and CRISPRa approaches. Thus, CRISPRa screening is a powerful tool for identifying novel engineering targets, facilitating the development of stress-resistant CHO cell lines, and enhancing therapeutic protein production.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3116–3126"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764217","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}

{"title":"Optimization of Malonyl Coenzyme A Biosensors in a Reconstituted Cell-Free System for Detecting Acetyl-CoA Carboxylase Activity","authors":"Shohei Ito,&nbsp;Shota Nishikawa,&nbsp;Naohiro Terasaka and Kosuke Fujishima*,&nbsp;","doi":"10.1021/acssynbio.5c00361","DOIUrl":"10.1021/acssynbio.5c00361","url":null,"abstract":"<p >Malonyl coenzyme A (malonyl-CoA) is a key precursor in the biosynthesis of fatty acids and polyketides, critical for industrial applications such as biofuel and pharmaceutical productions. Optimizing acetyl-CoA carboxylase (ACC), the enzyme that converts acetyl-CoA to malonyl-CoA, is essential for advancing metabolic engineering. Effective biosensors that detect malonyl-CoA levels are vital for high-throughput screening and directed evolution of ACC. Earlier efforts utilized the <i>Bacillus subtilis</i> FapR/FapO biosensor system in vivo to convert malonyl-CoA concentrations into fluorescent signals. However, <i>B. subtilis</i> biosensors suffered from narrow detection ranges, impeding accurate quantification across the concentrations needed to evaluate ACC activity, and were further limited by inconsistent cell viability, variable protein expression, and inability to directly supply acetyl-CoA. To address these challenges, we optimized a FapR/FapO biosensor tailored for the reconstituted cell-free protein synthesis system. By engineering the spacer sequence between the T7 promoter and the FapO operator, we developed an in vitro malonyl-CoA biosensor system with a broad detection range (50–1500 μM) with a boost in the maximum dynamic range reaching 95.3-fold at 1500 μM. Furthermore, we screened homologous FapR/FapO pairs from various Bacillota species, identifying the <i>Bacillus cytotoxicus</i> pair sensitive to low malonyl-CoA concentrations, exhibiting a maximum dynamic range of 96.6-fold at 500 μM. This renovated in vitro cell-free biosensor system enabled highly sensitive detection and precise quantification of single-chain, multidomain ACC-fusion protein activity in a reconstituted cell-free protein synthesis system, with the capacity to detect malonyl-CoA produced from as little as 100 pM of ACC-encoding DNA template. Overall, this platform offers a robust tool for the directed evolution and high-throughput screening of ACC, with a broad potential to enhance metabolic engineering and synthetic biology.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3245–3251"},"PeriodicalIF":3.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational Modulation of Plant Root Development Using Engineered Cytokinin Regulators","authors":"Rohan Rattan,&nbsp;Simon Alamos,&nbsp;Matthew Szarzanowicz,&nbsp;Kasey Markel and Patrick M. Shih*,&nbsp;","doi":"10.1021/acssynbio.5c00051","DOIUrl":"10.1021/acssynbio.5c00051","url":null,"abstract":"<p >Achieving precise control over quantitative developmental phenotypes is a key objective in plant biology. Recent advances in synthetic biology have enabled tools to reprogram entire developmental pathways; however, the complexity of designing synthetic genetic programs and the inherent interactions between various signaling processes remains a critical challenge. Here, we leverage Type-B response regulators to modulate the expression of genes involved in cytokinin-dependent growth and development processes. We rationally engineered these regulators to modulate their transcriptional activity (i.e., repression or activation) and potency while reducing their sensitivity to cytokinin. By localizing the expression of these engineered transcription factors using tissue-specific promoters, we can predictably tune cytokinin-regulated traits. As a proof of principle, we deployed this synthetic system in <i>Arabidopsis thaliana</i> to either decrease or increase the number of lateral roots. The simplicity and modularity of our approach makes it an ideal system for controlling other developmental phenotypes of agronomic interest in plants.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"3013–3023"},"PeriodicalIF":3.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.5c00051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Metabolic Engineering Strategies for the Production of Human Milk Oligosaccharides in Microbial Hosts","authors":"Hao Fang*,&nbsp;Jialun Gao,&nbsp;Nitesh Kumar Mund,&nbsp;Yu Tan,&nbsp;Peng Shi and Chen Zhao*,&nbsp;","doi":"10.1021/acssynbio.4c00867","DOIUrl":"10.1021/acssynbio.4c00867","url":null,"abstract":"<p >Human milk oligosaccharides (HMOs) are the third most abundant solid component in human breast milk, playing vital roles in promoting infant growth, supporting immune system development, and preventing infections. Due to these benefits, HMOs are increasingly being incorporated into infant formula, making their low-cost, large-scale production a pressing need. Recent advances in biosynthesis have focused on developing efficient production methods, particularly using genetically engineered <i>Escherichia coli</i> and other microbial hosts. This review begins by outlining the biological significance and structural complexity of HMOs, followed by an analysis of the limitations associated with traditional chemical and enzymatic synthesis approaches. The review then highlights the advantages of metabolic engineering in industrial microbes, such as reduced costs by eliminating the need for enzyme purification and leveraging native cellular pathways for sugar nucleotide biosynthesis. It further explores the construction of synthetic pathways for various HMOs in microbial systems, detailing metabolic engineering strategies including modular pathway design, cofactor optimization, glycosyltransferase and transporter engineering, and the spatial organization of enzymes through self-assembly techniques. Finally, the review addresses current challenges and future directions in the field. These include promoter engineering, further optimization of glycosyltransferases and transporters, balancing product synthesis with cell growth, and the integration of omics technologies and metabolic flux analysis. Overall, this review provides a comprehensive overview of HMO biosynthesis, emphasizing the integration of traditional metabolic engineering with synthetic and systems biology. This multilevel dynamic regulation approach is key to enabling the efficient and sustainable microbial production of HMOs.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 8","pages":"2885–2905"},"PeriodicalIF":3.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751817","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}