Synthetic and Systems Biotechnology最新文献

{"title":"High-level production of free fatty acids from lignocellulose hydrolysate by co-utilizing glucose and xylose in yeast","authors":"Xin Ni ,&nbsp;Jingjing Li ,&nbsp;Wei Yu ,&nbsp;Fan Bai ,&nbsp;Zongbao K. Zhao ,&nbsp;Jiaoqi Gao ,&nbsp;Fan Yang ,&nbsp;Yongjin J. Zhou","doi":"10.1016/j.synbio.2024.12.009","DOIUrl":"10.1016/j.synbio.2024.12.009","url":null,"abstract":"<div><div>Lignocellulose bio-refinery via microbial cell factories for chemical production represents a renewable and sustainable route in response to resource starvation and environmental concerns. However, the challenges associated with the co-utilization of xylose and glucose often hinders the efficiency of lignocellulose bioconversion. Here, we engineered yeast <em>Ogataea polymorpha</em> to effectively produce free fatty acids from lignocellulose. The non-oxidative branch of the pentose phosphate pathway, and the adaptive expression levels of xylose metabolic pathway genes <em>XYL1</em>, <em>XYL2</em> and <em>XYL3</em>, were systematically optimized. In addition, the introduction of xylose transporter and global regulation of transcription factors achieved synchronous co-utilization of glucose and xylose. The engineered strain produced 11.2 g/L FFAs from lignocellulose hydrolysates, with a yield of up to 0.054 g/g. This study demonstrated that metabolic rewiring of xylose metabolism could support the efficient co-utilization of glucose and xylose from lignocellulosic resources, which may provide theoretical reference for lignocellulose biorefinery.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 401-409"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047957","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":"Coupling genome-wide continuous perturbation with biosensor screening reveals the potential targets in yeast isopentanol synthesis network","authors":"Qi Xiao ,&nbsp;Jingjing Shi ,&nbsp;Lixian Wang ,&nbsp;Guoping Zhao ,&nbsp;Yanfei Zhang","doi":"10.1016/j.synbio.2024.12.010","DOIUrl":"10.1016/j.synbio.2024.12.010","url":null,"abstract":"<div><div>The increasing consumption of fossil fuels is contributing to global resource depletion and environmental pollution. Branched-chain higher alcohols, such as isopentanol and isobutanol, have attracted significant attention as next-generation biofuels. Biofuel production through microbial fermentation offers a green, sustainable, and renewable alternative to chemical synthesis. While enhanced production of isopentanol has been achieved in a variety of chassis, the fermentation yield has not yet reached levels suitable for industrial-scale production. In this study, we employed a continuous perturbation tool to construct a genome-scale perturbation library, combined with an isopentanol biosensor to screen for high-yielding mutants. We identified five high-yielding mutants, each exhibiting an increased glucose conversion rate and isopentanol titer. The F2 strain, in particular, achieved an isopentanol titer of 1.57 ± 0.014 g/L and a yield of 14.04 ± 0.251 mg/g glucose (10% glucose), surpassing the highest values reported to date in engineered <em>Saccharomyces cerevisiae</em>. Systematic transcriptome analysis of the isopentanol synthesis, glycolysis, glycerol metabolism, and ethanol synthesis pathways revealed that <em>MPC</em>, <em>OAC1</em>, <em>BAT2</em>, <em>GUT2</em>, <em>PDC6</em>, and <em>ALD4</em> are linked to efficient isopentanol production. Further analysis of differentially expressed genes (DEGs) identified 17 and 12 co-expressed DEGs (co-DEGs) in all mutants and the two second-round mutants, respectively. In addition, we validated the knockout or overexpression of key co-DEGs. Our results confirmed the critical roles of <em>HOM3</em> and <em>DIP5</em> in isopentanol production, along with genes associated with the aerobic respiratory chain (<em>SDH3</em>, <em>CYT1</em>, <em>COX7</em>, <em>ROX1</em>, and <em>ATG41</em>) and cofactor balance (<em>BNA2</em> and <em>NDE1</em>). Additionally, functional analysis of the co-DEGs revealed that <em>MAL33</em> is associated with the synthesis of branched-chain higher alcohols, expanding the intracellular metabolic network and offering new possibilities for green, cost-effective biofuel production.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 452-462"},"PeriodicalIF":4.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161058","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":"Design and structure of overlapping regions in PCA via deep learning","authors":"Yan Zheng ,&nbsp;Xi-Chen Cui ,&nbsp;Fei Guo ,&nbsp;Ming-Liang Dou ,&nbsp;Ze-Xiong Xie ,&nbsp;Ying-Jin Yuan","doi":"10.1016/j.synbio.2024.12.007","DOIUrl":"10.1016/j.synbio.2024.12.007","url":null,"abstract":"<div><div>Polymerase cycling assembly (PCA) stands out as the predominant method in the synthesis of kilobase-length DNA fragments. The design of overlapping regions is the core factor affecting the success rate of synthesis. However, there still exists DNA sequences that are challenging to design and construct in the genome synthesis. Here we proposed a deep learning model based on extensive synthesis data to discern latent sequence representations in overlapping regions with an AUPR of 0.805. Utilizing the model, we developed the SmartCut algorithm aimed at designing oligonucleotides and enhancing the success rate of PCA experiments. This algorithm was successfully applied to sequences with diverse synthesis constraints, 80.4 % of which were synthesized in a single round. We further discovered structure differences represented by major groove width, stagger, slide, and centroid distance between overlapping and non-overlapping regions, which elucidated the model's reasonableness through the lens of physical chemistry. This comprehensive approach facilitates streamlined and efficient investigations into the genome synthesis.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 442-451"},"PeriodicalIF":4.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161542","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":"Genetically-modified activation strategy facilitates the discovery of sesquiterpene-derived metabolites from Penicillium brasilianum","authors":"Wenni He ,&nbsp;Xiaoting Rong ,&nbsp;Hui Lv ,&nbsp;Lihua Zhang ,&nbsp;Jinglin Bai ,&nbsp;Lu Wang ,&nbsp;Liyan Yu ,&nbsp;Lixin Zhang ,&nbsp;Tao Zhang","doi":"10.1016/j.synbio.2024.12.006","DOIUrl":"10.1016/j.synbio.2024.12.006","url":null,"abstract":"<div><div>Genome mining has revealed that <em>Penicillium</em> spp. possess numerous down-regulated or cryptic biosynthetic gene clusters (BGCs). This finding hinted that our investigation of fungal secondary metabolomes is limited. Herein, we report a genetically-modified activation strategy to characterize the spectrum of sesquiterpenoids produced by <em>Penicillium brasilianum</em> CGMCC 3.4402. The cryptic or down-regulated pathways were stimulated by constitutive expression of pathway-specific regulator gene <em>berA</em> responsible for berkeleyacetals biosynthesis from <em>Neosartorya glabra</em>. Chemical analysis of the extracts from the mutant strain <em>Pb</em>-OE:<em>berA</em> enabled the isolation of two new compounds including one bisabolene-type arpenibisabolane C (<strong>1</strong>), one daucane-type arpenicarotane C (<strong>4</strong>), along with four known sesquiterpenoids including arpenibisabolane A (<strong>2</strong>), eupenicisirenins A (<strong>3</strong>), arpenicarotane B (<strong>5</strong>) and aspterric acid (<strong>6</strong>). The assignments of their structures were elucidated from detailed analyses of spectroscopic data, electronic circular dichroism calculation, and biogenetic considerations. The bioassay of isolated compounds (<strong>1</strong>–<strong>6</strong>) exhibited no cytotoxic activities against three tumor cells including MCF-7, HepG2, and A549. Arpenibisabolane C (<strong>1</strong>) and A (<strong>2</strong>) showed weak inhibition bioactivities on aquatic pathogens <em>Vibrio owensii</em> and <em>Vibrio algivorus</em>. Moreover, phylogenetic analysis and sequence alignments of crucial sesquiterpene synthases were performed. Based on the chemical structures and biogenetic investigations, a hypothetic pathway of new compounds (<strong>1</strong>, <strong>4</strong>) was proposed.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 391-400"},"PeriodicalIF":4.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011963","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":"Metabolic engineering of Glarea lozoyensis for high-level production of pneumocandin B0","authors":"Xinyi Zhang ,&nbsp;Shu Cheng ,&nbsp;Jing Yang ,&nbsp;Li Lu ,&nbsp;Zixin Deng ,&nbsp;Guangkai Bian ,&nbsp;Tiangang Liu","doi":"10.1016/j.synbio.2024.12.008","DOIUrl":"10.1016/j.synbio.2024.12.008","url":null,"abstract":"<div><div>Pneumocandin B₀ (PB₀) is a lipohexapeptide synthesized by <em>Glarea lozoyensis</em> and serves as the precursor for the widely used antifungal drug caspofungin acetate (Cancidas®). However, the low titer of PB₀ results in fermentation and purification costs during caspofungin production, limiting its widespread clinical application. Here, we engineered an efficient PB₀-producing strain of <em>G. lozoyensis</em> by systems metabolic engineering strategies, including multi-omics analysis and multilevel metabolic engineering. We overexpressed four rate-limiting enzymes: thioesterase GLHYD, two cytochrome P450s GLP450s, and chorismate synthase GLCS; knocked out two competing pathways responsible for producing 6-methylsalicylic acid and pyranidine E; and overexpressed the global transcriptional activator GLHYP. As a result, the PB₀ titer increased by 108.7 % to 2.63 g/L at the shake-flask level through combinatorial strategies. Our study provides valuable insights into achieving high-level production of PB₀ and offers general guidance for developing efficient fungal cell factories to produce polyketide synthase-non-ribosomal peptide synthetase hybrid metabolites.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 381-390"},"PeriodicalIF":4.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011966","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":"Environment signal dependent biocontainment systems for engineered organisms: Leveraging triggered responses and combinatorial systems","authors":"Shreya Varma ,&nbsp;Khushi Ash Gulati ,&nbsp;Janani Sriramakrishnan ,&nbsp;Riyaa Kedar Ganla ,&nbsp;Ritu Raval","doi":"10.1016/j.synbio.2024.12.005","DOIUrl":"10.1016/j.synbio.2024.12.005","url":null,"abstract":"<div><div>As synthetic biology advances, the necessity for robust biocontainment strategies for genetically engineered organisms (GEOs) grows increasingly critical to mitigate biosafety risks related to their potential environmental release. This paper aims to evaluate environment signal-dependent biocontainment systems for engineered organisms, focusing specifically on leveraging triggered responses and combinatorial systems. There are different types of triggers—chemical, light, temperature, and pH—this review illustrates how these systems can be designed to respond to environmental signals, ensuring a higher safety profile. It also focuses on combinatorial biocontainment to avoid consequences of unintended GEO release into an external environment. Case studies are discussed to demonstrate the practical applications of these systems in real-world scenarios.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 356-364"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011961","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":"Characterization of Aspergillus oryzae mutant and its application in heterologous lipase expression","authors":"Qinghua Li ,&nbsp;Chen Zhang ,&nbsp;Jianghua Li ,&nbsp;Guocheng Du ,&nbsp;Zhaofeng Li ,&nbsp;Jingwen Zhou ,&nbsp;Guoqiang Zhang","doi":"10.1016/j.synbio.2024.12.003","DOIUrl":"10.1016/j.synbio.2024.12.003","url":null,"abstract":"<div><div>The <em>Aspergillus oryzae</em> expression system has been developed into a chassis for the production of heterologous lipases, attributed to its strong capabilities in protein production and secretion, robust post-translational modifications, and favourable safety profile. However, the system's relatively low expression levels remain a challenge, hindering its ability to meet the increasing demands of large-scale production. Strain C19, screened by high-throughput methods combining droplet microfluidics and flow cytometry, was demonstrated to be a potential chassis cell based on fermentation kinetic analysis and transcriptome sequencing. By leveraging the endogenous α-amylase's expression elements and integration sites, a combination of random and site-directed integration strategies was employed to enhance the expression of heterologous lipases in strain C19. As a result, lipase production in shake-flask fermentation reached a titer of 113.6 U/L. The study further demonstrated that the different α-amylase gene loci could serve as effective integration sites for the multi-copy expression of heterologous proteins because the lipase activity of the 3-amylase site integrated strain C19#1-ABC was 3.3 times higher than that of C19#1. Furthermore, fermentation results in a 5-L bioreactor indicated that optimization of fermentation processes and facilities had the potential to further increase heterologous protein expression levels. These findings offered valuable insights into the advancement of <em>A. oryzae</em> expression systems and the potential for scaling engineered strains for industrial applications.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 365-372"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011903","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":"Enhancing abscisic acid production in Botrytis cinerea through metabolic engineering based on a constitutive promoter library","authors":"Ling-Ru Wang ,&nbsp;Ji-Zi-Hao Tang ,&nbsp;Shu-Ting Zhu ,&nbsp;Na Wu ,&nbsp;Zhi-Kui Nie ,&nbsp;Tian-Qiong Shi","doi":"10.1016/j.synbio.2024.12.004","DOIUrl":"10.1016/j.synbio.2024.12.004","url":null,"abstract":"<div><div>Abscisic acid (ABA) is an important plant growth regulator with broad applications in agriculture, forestry, and other fields. Currently, the industrial production of ABA primarily relies on microbial fermentation using <em>Botrytis cinerea</em>, but its genetic toolbox is limited. To address this, we first screened 10 strong constitutive promoters from the genome of <em>B. cinerea</em> through transcriptomic analysis. The expression levels of the promoters covered a range of 3–4 orders of magnitude according to the measured β-glucuronidase activity. Subsequently, four promoters of different strength were used to balance the cofactor supply in <em>B. cinerea</em>. Overexpression of NADH kinase using the medium-strength promoter <em>Pef1a</em> significantly enhanced ABA production, resulting in a 32.26 % increase compared to the control. Finally, by combining promoter engineering with a push-pull strategy, we optimized the biosynthesis of ABA. The recombinant strain Pthi4:hmgr-Pef1a:a4, overexpressing HMGR under the <em>Pthi4</em> promoter and Bcaba4 under the <em>Pef1a</em> promoter, achieved an ABA titer of 1.18 g/L, a 58.92 % increase. To our best knowledge, this is the first constitutive promoter library suitable for <em>B. cinerea</em>, providing important tools for the industrial production of ABA.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 373-380"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011959","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":"Modeling coding sequence design for virus-based expression in tobacco","authors":"Moritz Burghardt ,&nbsp;Tamir Tuller","doi":"10.1016/j.synbio.2024.12.002","DOIUrl":"10.1016/j.synbio.2024.12.002","url":null,"abstract":"<div><div>Transient expression in Tobacco is a popular way to produce recombinant proteins in plants. The design of various expression vectors, delivered into the plant by <em>Agrobacterium</em>, has enabled high production levels of some proteins. To further enhance expression, researchers often adapt the coding sequence of heterologous genes to the host, but this strategy has produced mixed results in Tobacco.</div><div>To study the effects of different sequence features on protein yield, we compile a dataset of the yields and coding sequences of previously published expression studies of more than 200 coding sequences.</div><div>We evaluate various established gene expression models on a subset of the expression studies. We find that use of tobacco codons is only moderately predictive of protein yield as informative sequence features likely extend over multiple codons. Additionally, we show that codon usage of organisms that use tobacco as a host for expression of their proteins in a similar way as the synthetic system, like viruses and agrobacteria, can be used to predict heterologous expression. Other predictive features are related to tRNA supply and demand, the inclusion of a translational ramp of codons with lower adaptation to the tRNA pool at the beginning of the coding region, and the amino acid composition of the recombinant protein. A model based on all the features achieved a correlation of 0.57 with protein yield.</div><div>We believe that our study provides a practical guideline for coding sequence design for efficient expression in tobacco.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 337-345"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971954","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":"Construction of antibiotic-free riboflavin producer in Escherichia coli by metabolic engineering strategies with a plasmid stabilization system","authors":"Xiaoling Zhang ,&nbsp;Yanan Li ,&nbsp;Kang Wang ,&nbsp;Jilong Yin ,&nbsp;Yuxuan Du ,&nbsp;Zhen Yang ,&nbsp;Xuewei Pan ,&nbsp;Jiajia You ,&nbsp;Zhiming Rao","doi":"10.1016/j.synbio.2024.12.001","DOIUrl":"10.1016/j.synbio.2024.12.001","url":null,"abstract":"<div><div>Riboflavin, an important vitamin utilized in pharmaceutical products and as a feed additive, is mainly produced by metabolically engineered bacterial fermentation. However, the reliance on antibiotics in the production process leads to increased costs and safety risks. To address these challenges, an antibiotic-free <em>Escherichia coli</em> riboflavin producer was constructed using metabolic engineering approaches coupled with a novel plasmid stabilization system. Initially, competitive pathways and feedback inhibition were attenuated to enhance the metabolic flux towards riboflavin. Key genes in the purine pathway were overexpressed to boost the availability of riboflavin precursors. Subsequently, a plasmid stabilization system based on toxin was screened and characterized, achieving a plasmid retention rate of 84.9% after 10 days of passaging. Finally, transcriptomic analysis at the genome-wide level revealed several rate-limiting genes, including <em>pgl</em>, <em>gnd</em>, and <em>yigB</em>, which were subsequently upregulated, leading to a 26% improvement in riboflavin production. With optimization of the culture medium, the final strain allowed the production of 11.5 g/L of riboflavin with a yield of 90.4 mg/g glucose in 5 L bioreactors without antibiotics. These strategies can be extended to other plasmid-based riboflavin derivative production systems.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 346-355"},"PeriodicalIF":4.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984877","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}