{"title":"A systematic discussion and comparison of the construction methods of synthetic microbial community","authors":"Chenglong Li, Yanfeng Han, Xiao Zou, Xueqian Zhang, Qingsong Ran, Chunbo Dong","doi":"10.1016/j.synbio.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.006","url":null,"abstract":"<div><p>Synthetic microbial community has widely concerned in the fields of agriculture, food and environment over the past few years. However, there is little consensus on the method to synthetic microbial community from construction to functional verification. Here, we review the concept, characteristics, history and applications of synthetic microbial community, summarizing several methods for synthetic microbial community construction, such as isolation culture, core microbiome mining, automated design, and gene editing. In addition, we also systematically summarized the design concepts, technological thresholds, and applicable scenarios of various construction methods, and highlighted their advantages and limitations. Ultimately, this review provides four efficient, detailed, easy-to-understand and -follow steps for synthetic microbial community construction, with major implications for agricultural practices, food production, and environmental governance.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 775-783"},"PeriodicalIF":4.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000954/pdfft?md5=1ce7685783df1d9189ef567863d52d18&pid=1-s2.0-S2405805X24000954-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438590","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}
Shupeng Ruan , Yuxin Yang , Xinying Zhang , Guanjuan Luo , Ying Lin , Shuli Liang
{"title":"Screening and characterization of integration sites based on CRISPR-Cpf1 in Pichia pastoris","authors":"Shupeng Ruan , Yuxin Yang , Xinying Zhang , Guanjuan Luo , Ying Lin , Shuli Liang","doi":"10.1016/j.synbio.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.002","url":null,"abstract":"<div><p><em>Pichia pastoris</em>, a methylotrophic yeast, can utilize methanol as a carbon source and energy source to synthesize high-value chemicals, and is an ideal host for biomanufacturing. Constructing the <em>P</em>. <em>pastoris</em> cell factory is somewhat impeded due to the absence of genetic tools for manipulating multi-gene biosynthetic pathways. To broaden its application in the field of metabolic engineering, this study identified and screened 15 novel integration sites in <em>P. pastoris</em> using CRISPR-Cpf1 genome editing technology, with EGFP serving the reporter protein. These integration sites have integration efficiencies of 10–100 % and varying expression strengths, which allow for selection based on the expression levels of genes as needed. Additionally, these integrated sites are applied in the heterologous biosynthesis of <em>P. pastoris</em>, such as the astaxanthin biosynthetic pathway and the carbon dioxide fixation pathway of the Calvin-Benson-Bassham (CBB) cycle. During the three-site integration process, the 8 genes of the CBB cycle were integrated into the genome of <em>P. pastoris</em>. This indicates the potential of these integration sites for integrating large fragments and suggests their successful application in metabolic engineering of <em>P. pastoris</em>. This may lead to improved efficiency of genetic engineering in <em>P. pastoris</em>.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 759-765"},"PeriodicalIF":4.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000917/pdfft?md5=bf68a535595642f9f0268209b4e5ebfb&pid=1-s2.0-S2405805X24000917-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429022","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}
Shan Li , Shuangshuang Luo , Xinran Yin , Xingying Zhao , Xuyang Wang , Song Gao , Sha Xu , Jian Lu , Jingwen Zhou
{"title":"Screening of ent-copalyl diphosphate synthase and metabolic engineering to achieve de novo biosynthesis of ent-copalol in Saccharomyces cerevisiae","authors":"Shan Li , Shuangshuang Luo , Xinran Yin , Xingying Zhao , Xuyang Wang , Song Gao , Sha Xu , Jian Lu , Jingwen Zhou","doi":"10.1016/j.synbio.2024.06.005","DOIUrl":"https://doi.org/10.1016/j.synbio.2024.06.005","url":null,"abstract":"<div><p>The diterpene <em>ent</em>-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta <em>(Andrographis paniculata)</em>. <em>De novo</em> biosynthesis of <em>ent</em>-copalol has not been reported, because the catalytic activity of <em>ent</em>-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of <em>ent</em>-copalol, <em>Saccharomyces cerevisiae</em> was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of <em>ent</em>-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length <em>Ap</em>CPSs were screened by transcriptome sequencing of <em>A. paniculata</em> and <em>Ap</em>CPS2 had the best activity and produced <em>ent</em>-CPP exclusively. The peak area of <em>ent</em>-copalol was increased after the <em>Ap</em>CPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L <em>ent</em>-copalol was generated. In this study, <em>de novo</em> biosynthesis and identification of <em>ent</em>-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"9 4","pages":"Pages 784-792"},"PeriodicalIF":4.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24000942/pdfft?md5=d092e35682132d8845904ea2be622283&pid=1-s2.0-S2405805X24000942-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438591","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}
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}