Huang Xie , Yi-Ting Su , Qing-Ting Bu , Yue-Ping Li , Qing-Wei Zhao , Yi-Ling Du , Yong-Quan Li
{"title":"Stepwise increase of fidaxomicin in an engineered heterologous host Streptomyces albus through multi-level metabolic engineering","authors":"Huang Xie , Yi-Ting Su , Qing-Ting Bu , Yue-Ping Li , Qing-Wei Zhao , Yi-Ling Du , Yong-Quan Li","doi":"10.1016/j.synbio.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.004","url":null,"abstract":"<div><p>The anti-<em>Clostridium difficile</em> infection (CDI) drug fidaxomicin is a natural polyketide metabolite mainly produced by <em>Micromonosporaceae</em>, such as <em>Actinoplanes deccanensis</em>, <em>Dactylosporangium aurantiacum</em>, and <em>Micromonospora echinospora</em>. In the present study, we employed a stepwise strategy by combining heterologous expression, chassis construction, promoter engineering, activator and transporters overexpression, and optimization of fermentation media for high-level production of fidaxomicin. The maximum yield of 384 mg/L fidaxomicin was achieved with engineered <em>Streptomyces albus</em> D7-VHb in 5 L-tank bioreactor, and it was approximately 15-fold higher than the native strain <em>Actinoplanes deccanensis</em> YP-1 with higher strain stability and growth rate. This study developed an enhanced chassis strain, and for the first time, achieved the heterologous synthesis of fidaxomicin through a combinatorial metabolic engineering strategy.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 766-774"},"PeriodicalIF":4.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000930/pdfft?md5=4fd3723f7f03aec6b89d38dd4dbe80ea&pid=1-s2.0-S2405805X24000930-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438589","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}
Xiaodi Wang , Junyuan Hou , Jieyao Cui , Zhiwen Wang , Tao Chen
{"title":"Engineering Corynebacterium glutamicum for the efficient production of 3-hydroxypropionic acid from glucose via the β-alanine pathway","authors":"Xiaodi Wang , Junyuan Hou , Jieyao Cui , Zhiwen Wang , Tao Chen","doi":"10.1016/j.synbio.2024.06.003","DOIUrl":"10.1016/j.synbio.2024.06.003","url":null,"abstract":"<div><p>3-Hydroxypropionic Acid (3-HP) is recognized as a high value-added chemical with a broad range of applications. Among the various biosynthetic pathways for 3-HP production, the β-alanine pathway is particularly noteworthy due to its capacity to generate 3-HP from glucose at a high theoretical titer. In this study, the β-alanine biosynthesis pathway was introduced and optimized in <em>Corynebacterium glutamicum</em>. By strategically regulating the supply of precursors, we successfully engineered a strain capable of efficiently synthesizing 3-HP through the β-alanine pathway, utilizing glucose as the substrate. The engineered strain CgP36 produced 47.54 g/L 3-HP at a yield of 0.295 g/g glucose during the fed-batch fermentation in a 5 L fermenter, thereby attaining the highest 3-HP titer obtained from glucose via the β-alanine pathway.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 752-758"},"PeriodicalIF":4.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000929/pdfft?md5=8bb95ceac18d0aae0a7c25805ea52fc6&pid=1-s2.0-S2405805X24000929-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141413593","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}
Xinglong Wang , Shuyao Yu , Ruoxi Sun , Kangjie Xu , Kun Wang , Ruiyan Wang , Junli Zhang , Wenwen Tao , Shangyang Yu , Kai Linghu , Xinyi Zhao , Jingwen Zhou
{"title":"Identification of a human type XVII collagen fragment with high capacity for maintaining skin health","authors":"Xinglong Wang , Shuyao Yu , Ruoxi Sun , Kangjie Xu , Kun Wang , Ruiyan Wang , Junli Zhang , Wenwen Tao , Shangyang Yu , Kai Linghu , Xinyi Zhao , Jingwen Zhou","doi":"10.1016/j.synbio.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.001","url":null,"abstract":"<div><p>Collagen XVII (COL17) is a transmembrane protein that mediates skin homeostasis. Due to expression of full length collagen was hard to achieve in microorganisms, arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis. Here, COL17 fragments (27–33 amino acids) were extracted and replicated 16 times for recombinant expression in <em>Escherichia coli</em>. Five variants were soluble expressed, with the highest yield of 223 mg/L. The fusion tag was removed for biochemical and biophysical characterization. Circular dichroism results suggested one variant (sample-1707) with a triple-helix structure at >37 °C. Sample-1707 can assemble into nanofiber (width, 5.6 nm) and form hydrogel at 3 mg/mL. Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation. Furthermore, sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration, demonstrating a high capacity to induce skin cell regeneration and promote wound healing. A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of >30 % higher than simply using chitosan. Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L. These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 733-741"},"PeriodicalIF":4.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000905/pdfft?md5=08d360192ff10c173b508a8e2020684f&pid=1-s2.0-S2405805X24000905-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141292050","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}
Yimeng Zuo , Minghui Zhao , Yuanwei Gou , Lei Huang , Zhinan Xu , Jiazhang Lian
{"title":"Transportation engineering for enhanced production of plant natural products in microbial cell factories","authors":"Yimeng Zuo , Minghui Zhao , Yuanwei Gou , Lei Huang , Zhinan Xu , Jiazhang Lian","doi":"10.1016/j.synbio.2024.05.014","DOIUrl":"10.1016/j.synbio.2024.05.014","url":null,"abstract":"<div><p>Plant natural products (PNPs) exhibit a wide range of biological activities and have essential applications in various fields such as medicine, agriculture, and flavors. Given their natural limitations, the production of high-value PNPs using microbial cell factories has become an effective alternative in recent years. However, host metabolic burden caused by its massive accumulation has become one of the main challenges for efficient PNP production. Therefore, it is necessary to strengthen the transmembrane transport process of PNPs. This review introduces the discovery and mining of PNP transporters to directly mediate PNP transmembrane transportation both intracellularly and extracellularly. In addition to transporter engineering, this review also summarizes several auxiliary strategies (such as small molecules, environmental changes, and vesicles assisted transport) for strengthening PNP transportation. Finally, this review is concluded with the applications and future perspectives of transportation engineering in the construction and optimization of PNP microbial cell factories.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 742-751"},"PeriodicalIF":4.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000899/pdfft?md5=b7bb66ebe606a02e837a92d342ff7e2b&pid=1-s2.0-S2405805X24000899-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141277296","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":"Overexpression of arginase gene CAR1 renders yeast Saccharomyces cerevisiae acetic acid tolerance","authors":"Liang Xiong , Ya-Ting Wang , Ming-Hai Zhou , Hiroshi Takagi , Jiufu Qin , Xin-Qing Zhao","doi":"10.1016/j.synbio.2024.05.013","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.05.013","url":null,"abstract":"<div><p>Acetic acid is a common inhibitor present in lignocellulose hydrolysate, which inhibits the ethanol production by yeast strains. Therefore, the cellulosic ethanol industry requires yeast strains that can tolerate acetic acid stress. Here we demonstrate that overexpressing a yeast native arginase-encoding gene, <em>CAR1</em>, renders <em>Saccharomyces cerevisiae</em> acetic acid tolerance. Specifically, ethanol yield increased by 27.3% in the <em>CAR1</em>-overexpressing strain compared to the control strain under 5.0 g/L acetic acid stress. The global intracellular amino acid level and compositions were further analyzed, and we found that <em>CAR1</em> overexpression reduced the total amino acid content in response to acetic acid stress. Moreover, the <em>CAR1</em> overexpressing strain showed increased ATP level and improved cell membrane integrity. Notably, we demonstrated that the effect of <em>CAR1</em> overexpression was independent of the spermidine and proline metabolism, which indicates novel mechanisms for enhancing yeast stress tolerance. Our studies also suggest that <em>CAR1</em> is a novel genetic element to be used in synthetic biology of yeast for efficient production of fuel ethanol.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 723-732"},"PeriodicalIF":4.8,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000887/pdfft?md5=47276d74cdb3e5d76a16b360e1eaa356&pid=1-s2.0-S2405805X24000887-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242384","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":"Digitoxose as powerful glycosyls for building multifarious glycoconjugates of natural products and un-natural products","authors":"Kemeng Li , Zhengyan Guo , Liping Bai","doi":"10.1016/j.synbio.2024.05.012","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.05.012","url":null,"abstract":"<div><p>Digitoxose, a significant 2,6-dideoxyhexose found in nature, exists in many small-molecule natural products. These digitoxose-containing natural products can be divided into steroids, macrolides, macrolactams, anthracyclines, quinones, enediynes, acyclic polyene, indoles and oligosaccharides, that exhibit antibacterial, anti-viral, antiarrhythmic, and antitumor activities respectively. As most of digitoxose-containing natural products for clinical application or preclinical tests, this review also summarizes the biosynthesis of digitoxose, and application of compound diversification by introducing sugar plasmids. It may provide a practical approach to expanding the diversity of digitoxose-containing products.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 701-712"},"PeriodicalIF":4.8,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000875/pdfft?md5=f50d11b738c04b4ac049e9e7ca8fea83&pid=1-s2.0-S2405805X24000875-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242373","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}
Jinqi Shi , Chen Deng , Chunyue Zhang , Shu Quan , Liqiang Fan , Liming Zhao
{"title":"Combinatorial metabolic engineering of Escherichia coli for de novo production of structurally defined and homogeneous Amino oligosaccharides","authors":"Jinqi Shi , Chen Deng , Chunyue Zhang , Shu Quan , Liqiang Fan , Liming Zhao","doi":"10.1016/j.synbio.2024.05.011","DOIUrl":"10.1016/j.synbio.2024.05.011","url":null,"abstract":"<div><p>Amino oligosaccharides (AOs) possess various biological activities and are valuable in the pharmaceutical, food industries, and agriculture. However, the industrial manufacturing of AOs has not been realized yet, despite reports on physical, chemical, and biological approaches. In this study, the <em>de novo</em> production of chitin oligosaccharides (CHOS), a type of structurally defined AOs, was achieved in <em>Escherichia coli</em> through combinatorial pathway engineering. The most suitable glycosyltransferase for CHOS production was found to be NodCL from <em>Mesorhizobium Loti</em>. Then, by knocking out the <em>nagB</em> gene to block the flow of N-acetyl-<span>d</span>-glucosamine (NAG) to the glycolytic pathway in <em>E. coli</em> and adjusting the copy number of NodCL-coding gene, the CHOS yield was increased by 6.56 times. Subsequently, by introducing of UDP-N-acetylglucosamine (UDP-GlcNAc) <em>salvage</em> pathway for and optimizing fermentation conditions, the yield of CHOS reached 207.1 and 468.6 mg/L in shake-flask cultivation and a 5-L fed-batch bioreactor, respectively. Meanwhile, the concentration of UDP-GlcNAc was 91.0 mg/L, the highest level reported in <em>E. coli</em> so far. This study demonstrated, for the first time, the production of CHOS with distinct structures in plasmid-free <em>E. coli</em>, laying the groundwork for the biosynthesis of CHOS and providing a starting point for further engineering and commercial production.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 713-722"},"PeriodicalIF":4.8,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000863/pdfft?md5=5c0ca8265585c2434e8e346f77cfebf0&pid=1-s2.0-S2405805X24000863-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136653","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}
Caixia Tan , Yuanyuan xiao , Ting Liu , Siyao Chen , Juan Zhou , Sisi Zhang , Yiran Hu , Anhua Wu , Chunhui Li
{"title":"Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches","authors":"Caixia Tan , Yuanyuan xiao , Ting Liu , Siyao Chen , Juan Zhou , Sisi Zhang , Yiran Hu , Anhua Wu , Chunhui Li","doi":"10.1016/j.synbio.2024.05.008","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.05.008","url":null,"abstract":"<div><p><em>Clostridioides difficile</em> (<em>C. difficile</em>), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for <em>Clostridioides difficile</em> infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against <em>C. difficile</em> is of paramount importance. In our study, the complete proteome sequences of 118 strains of <em>C. difficile</em> were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 667-683"},"PeriodicalIF":4.8,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000838/pdfft?md5=c0004b11a30ad7b49ee9863aa380bea4&pid=1-s2.0-S2405805X24000838-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073091","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":"A generative benchmark for evaluating the performance of fluorescent cell image segmentation","authors":"Jun Tang , Wei Du , Zhanpeng Shu , Zhixing Cao","doi":"10.1016/j.synbio.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.05.005","url":null,"abstract":"<div><p>Fluorescent cell imaging technology is fundamental in life science research, offering a rich source of image data crucial for understanding cell spatial positioning, differentiation, and decision-making mechanisms. As the volume of this data expands, precise image analysis becomes increasingly critical. Cell segmentation, a key analysis step, significantly influences quantitative analysis outcomes. However, selecting the most effective segmentation method is challenging, hindered by existing evaluation methods' inaccuracies, lack of graded evaluation, and narrow assessment scope. Addressing this, we developed a novel framework with two modules: StyleGAN2-based contour generation and Pix2PixHD-based image rendering, producing diverse, graded-density cell images. Using this dataset, we evaluated three leading cell segmentation methods: DeepCell, CellProfiler, and CellPose. Our comprehensive comparison revealed CellProfiler's superior accuracy in segmenting cytoplasm and nuclei. Our framework diversifies cell image data generation and systematically addresses evaluation challenges in cell segmentation technologies, establishing a solid foundation for advancing research and applications in cell image analysis.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 627-637"},"PeriodicalIF":4.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000802/pdfft?md5=13815bcd26120681d6104aa2879c4302&pid=1-s2.0-S2405805X24000802-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950918","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}
Xiao Wen , Jiawei Lin , Chunhe Yang , Ying Li , Haijiao Cheng , Ye Liu , Yue Zhang , Hongwu Ma , Yufeng Mao , Xiaoping Liao , Meng Wang
{"title":"Automated characterization and analysis of expression compatibility between regulatory sequences and metabolic genes in Escherichia coli","authors":"Xiao Wen , Jiawei Lin , Chunhe Yang , Ying Li , Haijiao Cheng , Ye Liu , Yue Zhang , Hongwu Ma , Yufeng Mao , Xiaoping Liao , Meng Wang","doi":"10.1016/j.synbio.2024.05.010","DOIUrl":"10.1016/j.synbio.2024.05.010","url":null,"abstract":"<div><p>Utilizing standardized artificial regulatory sequences to fine-tuning the expression of multiple metabolic pathways/genes is a key strategy in the creation of efficient microbial cell factories. However, when regulatory sequence expression strengths are characterized using only a few reporter genes, they may not be applicable across diverse genes. This introduces great uncertainty into the precise regulation of multiple genes at multiple expression levels. To address this, our study adopted a fluorescent protein fusion strategy for a more accurate assessment of target protein expression levels. We combined 41 commonly-used metabolic genes with 15 regulatory sequences, yielding an expression dataset encompassing 520 unique combinations. This dataset highlighted substantial variation in protein expression level under identical regulatory sequences, with relative expression levels ranging from 2.8 to 176-fold. It also demonstrated that improving the strength of regulatory sequences does not necessarily lead to significant improvements in the expression levels of target proteins. Utilizing this dataset, we have developed various machine learning models and discovered that the integration of promoter regions, ribosome binding sites, and coding sequences significantly improves the accuracy of predicting protein expression levels, with a Spearman correlation coefficient of 0.72, where the promoter sequence exerts a predominant influence. Our study aims not only to provide a detailed guide for fine-tuning gene expression in the metabolic engineering of <em>Escherichia coli</em> but also to deepen our understanding of the compatibility issues between regulatory sequences and target genes.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 647-657"},"PeriodicalIF":4.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000851/pdfft?md5=f535dd3094336720674eaf7d8d922be9&pid=1-s2.0-S2405805X24000851-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141042170","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}