Synthetic and Systems Biotechnology最新文献

{"title":"Transcriptome analysis reveals methanol metabolism variations for the growth damage caused by overexpression of chimeric transactivators in Pichia pastoris","authors":"Qi Liu ,&nbsp;Ziyu He ,&nbsp;Menghao Cai","doi":"10.1016/j.synbio.2024.09.008","DOIUrl":"10.1016/j.synbio.2024.09.008","url":null,"abstract":"<div><div>Methanol is a promising substrate for sustainable biomanufacturing, and <em>Pichia pastoris</em> has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter. Previous reconstruction of gene circuits highly improved transcriptional activity, but excessive expression of chimeric transactivator damaged cell growth on methanol. Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regulatory networks. The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism, especially the <em>alcohol oxidase 1</em> (<em>AOX1</em>), but without remarkable changes in expression of transcriptional factors. Meanwhile, the synthesis of peroxisomes also varied with chimeric transactivator expression. In addition, the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism. The gene expression patterns caused by different expression levels of chimeric transactivators have also been clarified. This work provides useful information to understand the transcriptional regulation of the <em>AOX1</em> promoter and methanol signaling. It revealed the importance of balancing transcription factor expression for the host improvement.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 133-139"},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445509","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":"Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi","authors":"Zhengping Li ,&nbsp;Yuhong Gan ,&nbsp;Changyu Gou ,&nbsp;Qiongyu Ye ,&nbsp;Yang Wu ,&nbsp;Yuhong Wu ,&nbsp;Tingxing Yang ,&nbsp;Baolian Fan ,&nbsp;Aijia Ji ,&nbsp;Qi Shen ,&nbsp;Lixin Duan","doi":"10.1016/j.synbio.2024.09.005","DOIUrl":"10.1016/j.synbio.2024.09.005","url":null,"abstract":"<div><div><em>Artemisia argyi</em> H. Lév. &amp; Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of <em>A. argyi</em>, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in <em>A. argyi</em> remains underexplored. In this study, we identified four <em>β</em>-caryophyllene synthases from <em>A. argyi.</em> A high-yield <em>β</em>-caryophyllene engineered <em>Saccharomyces cerevisiae</em> cell factory has been built in this study. By fusing <em>ERG20</em> and <em>AarTPS88</em> with a flexible linker (GGGS)₂ and enhancing metabolic flux in the MVA pathway (<em>HIF-1</em>, <em>tHMGR</em>, and <em>UPC2-1</em>), we achieved a titer of <em>β</em>-caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of <em>β</em>-caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of <em>β</em>-caryophyllene.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 158-164"},"PeriodicalIF":4.4,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533920","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":"Development of a green Komagataella phaffii cell factory for sustainable production of plant-derived sesquiterpene (–)-α-bisabolol","authors":"Jintao Cheng ,&nbsp;Zhongji Pu ,&nbsp;Jiali Chen ,&nbsp;Dingfeng Chen ,&nbsp;Baoxian Li ,&nbsp;Zhengshun Wen ,&nbsp;Yuanxiang Jin ,&nbsp;Yanlai Yao ,&nbsp;Kan Shao ,&nbsp;Xiaosong Gu ,&nbsp;Guiling Yang","doi":"10.1016/j.synbio.2024.09.006","DOIUrl":"10.1016/j.synbio.2024.09.006","url":null,"abstract":"<div><div>(–)-α-Bisabolol is a plant-derived sesquiterpene derived from <em>Eremanthus erythropappus,</em> which can be used as a raw material in cosmetics and has anti-inflammatory function. In this study, we designed six mutation sites of the (–)-α-bisabolol synthase BOS using the plmDCA algorithm. Among these, the F324Y mutation demonstrated exceptional performance, increasing the product yield by 73 %. We constructed a <em>de novo</em> (–)-α-bisabolol biosynthesis pathways through systematic synthetic biology strategies, including the enzyme design of BOS, selection of different linkers in fusion expression, and optimization of the mevalonate pathway, weakening the branching metabolic flow and multi-copy strategies, the yield of (–)-α-bisabolol was significantly increased, which was nearly 35-fold higher than that of the original strain (2.03 mg/L). The engineered strain was capable of producing 69.7 mg/L in shake flasks. To the best of our knowledge, this is the first report on the biosynthesis of (–)-α-bisabolol in <em>Komagataella phaffii</em>, implying this is a robust cell factory for sustainable production of other terpenoids.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 120-126"},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445489","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":"Functional investigation of the SAM-dependent methyltransferase RdmB in anthracycline biosynthesis","authors":"Moli Sang ,&nbsp;Qingyu Yang ,&nbsp;Jiawei Guo ,&nbsp;Peiyuan Feng ,&nbsp;Wencheng Ma ,&nbsp;Wei Zhang","doi":"10.1016/j.synbio.2024.09.002","DOIUrl":"10.1016/j.synbio.2024.09.002","url":null,"abstract":"<div><p>A novel sub-class of <em>S</em>-adenosyl-<span>l</span>-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from <em>Streptomyces purpurascens,</em> it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4-<em>O</em>-methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4-<em>O</em>-methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 102-109"},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001212/pdfft?md5=2b156fbb5e3c9f4fbd7f97ed291fe436&pid=1-s2.0-S2405805X24001212-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168410","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":"Predicting effective drug combinations for cancer treatment using a graph-based approach","authors":"Qi Wang ,&nbsp;Xiya Liu ,&nbsp;Guiying Yan","doi":"10.1016/j.synbio.2024.09.003","DOIUrl":"10.1016/j.synbio.2024.09.003","url":null,"abstract":"<div><div>Drug combination therapy, involving the use of two or more drugs, has been widely employed to treat complex diseases such as cancer. It enhances therapeutic efficacy, reduces drug resistance, and minimizes side effects. However, traditional methods to identify effective drug combinations are time-consuming, costly, and less efficient than computational methods. Therefore, developing computational approaches to predict drug combinations has become increasingly important.</div><div>In this paper, we developed the Random Walk with Restart for Drug Combination (RWRDC) model to predict effective drug combinations for cancer therapy. The RWRDC model offers a quantitative mathematical method for predicting the potential effective drug combinations. Cross-validation results indicate that the RWRDC model outperforms other predictive models, particularly in breast, colorectal, and lung cancer predictions across various performance metrics. We have theoretically proven the convergence of its algorithm and provided an explanation for the algorithm's rationality. A targeted case study on breast cancer further highlights the capability of RWRDC to identify effective drug combinations. These findings highlight our model as a novel and effective tool for discovering potential effective drug combinations, offering new possibilities in therapy. Additionally, the graph-based framework of RWRDC holds potential for predicting drug combinations in other complex diseases, expanding its utility in the medical field.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 148-155"},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445486","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":"Assessing the physiological properties of baker's yeast based on single-cell Raman spectrum technology","authors":"Xi Sun ,&nbsp;Xin Zhou ,&nbsp;Ran Yu ,&nbsp;Xiaofang Zhou ,&nbsp;Jun Zhang ,&nbsp;Teng Xu ,&nbsp;Jianmei Wang ,&nbsp;Mengqi Li ,&nbsp;Xiaoting Li ,&nbsp;Min Zhang ,&nbsp;Jian Xu ,&nbsp;Jia Zhang","doi":"10.1016/j.synbio.2024.09.004","DOIUrl":"10.1016/j.synbio.2024.09.004","url":null,"abstract":"<div><div>With rapid progress in the yeast fermentation industry, a comprehensive commercial yeast quality assessment approach integrating efficiency, accuracy, sensitivity, and cost-effectiveness is required. In this study, a new yeast quality assessment method based on single-cell Raman technology was developed and contrasted with traditional methods. The findings demonstrated significant associations (Pearson correlation coefficient of 0.933 on average) between the two methods in measuring physiological indicators, including cell viability and intracellular trehalose content, demonstrating the credibility of the Raman method compared to the traditional method. Furthermore, the sensitivity of the Raman method in viable but non-culturable cells was higher in measuring yeast cell viability (17.9 % more sensitive). According to the accurate quantitative analysis of metabolic activity level (MAL) of yeast cells, the cell vitality was accurately quantified at population and single-cell levels, offering a more comprehensive assessment of yeast fermentation performance. Overall, the single-cell Raman method integrates credibility, feasibility, accuracy, and sensitivity in yeast quality assessment, offering a new technological framework for quality assessments of live-cell yeast products.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 110-118"},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441270","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":"Engineered probiotic-mediated intratumoral delivery and controlled release of bacterial collagenase for cancer therapy","authors":"Hong-Rui Li,&nbsp;Bang-Ce Ye","doi":"10.1016/j.synbio.2024.09.001","DOIUrl":"10.1016/j.synbio.2024.09.001","url":null,"abstract":"<div><div>Elevated collagen levels within breast tumors are strongly associated with tumor progression and present a barrier to effective therapeutic agent penetration within the tumor microenvironment (TME), leading to poor clinical outcomes. To address this challenge, we engineered a probiotic strain to degrade collagen within the TME by selectively colonizing in tumors and releasing bacterial collagenase in a lysis-dependent manner. Initially, we constructed a therapeutic bacterial strain designed to lyse within the TME and release an encoded immunotoxin comprising a nanobody targeting CD47 (CD47nb) and a modified <em>Pseudomonas</em> exotoxin A (PE38KDEL). The introduction of collagenase-expressing bacteria, in conjunction with therapeutic immunotoxin, reduced collagen fiber levels within the TME, resulting in inhibited tumor growth and prolonged survival in a murine model of breast cancer. Furthermore, we investigated the broader applicability of the collagenase-expressing bacterial strain in combination with chemotherapeutic drugs, such as doxorubicin. Remarkably, synergistic antitumor effects were observed in mice treated with this combination therapy. In conclusion, our study demonstrates that probiotic delivery of bacterial collagenase offers a promising adjuvant treatment strategy for selectively degrading intratumoral collagen, thereby improving the efficacy of anticancer therapies in breast cancer.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 226-236"},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142659617","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":"Tissue chips as headway model and incitement technology","authors":"Prerna Suchitan Modi ,&nbsp;Abhishek Singh ,&nbsp;Awyang Chaturvedi ,&nbsp;Shailly Agarwal ,&nbsp;Raghav Dutta ,&nbsp;Ranu Nayak ,&nbsp;Alok Kumar Singh","doi":"10.1016/j.synbio.2024.08.007","DOIUrl":"10.1016/j.synbio.2024.08.007","url":null,"abstract":"<div><p>Tissue on a chip or organ-on-chip (OOC) is a technology that's dignified to form a transformation in drug discovery through the use of advanced platforms. These are 3D in<em>-vitro</em> cell culture models that mimic micro-environment of human organs or tissues on artificial microstructures built on a portable microfluidic chip without involving sacrificial humans or animals.</p><p>This review article aims to offer readers a thorough and insightful understanding of technology. It begins with an in-depth understanding of chip design and instrumentation, underlining its pivotal role and the imperative need for its development in the modern scientific landscape. The review article explores into the myriad applications of OOC technology, showcasing its transformative impact on fields such as radiobiology, drug discovery and screening, and its pioneering use in space research. In addition to highlighting these diverse applications, the article provides a critical analysis of the current challenges that OOC technology faces. It examines both the biological and technical limitations that hinder its progress and efficacy and discusses the potential advancements and innovations that could drive the OOC technology forward. Through this comprehensive review, readers will gain a deep appreciation of the significance, capabilities, and evolving landscape of OOC technology.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 86-101"},"PeriodicalIF":4.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001182/pdfft?md5=fdd969b5051ee124e51a362370907009&pid=1-s2.0-S2405805X24001182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096001","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":"Engineering the TetR-family transcriptional regulator XNR_0706 to enhance heterologous spinosad production in Streptomyces albus B4 chassis","authors":"Xingjun Cui ,&nbsp;Hao Tang ,&nbsp;Wenzong Wang ,&nbsp;Wenping Wei ,&nbsp;Jing Wu ,&nbsp;Bang-Ce Ye","doi":"10.1016/j.synbio.2024.08.008","DOIUrl":"10.1016/j.synbio.2024.08.008","url":null,"abstract":"<div><div>The TetR family of regulators are an important group of transcription regulators that regulate diverse cellular processes in prokaryotes. In this study, we found that XNR_0706, a TetR family regulator, controlled the expression of <em>XNR_0345</em>, <em>XNR_0454</em>, <em>XNR_0513</em> and <em>XNR_1438</em> putatively involved in fatty acid β-oxidation by interacting with the promoter regions in <em>Streptomyces albus</em> B4. The transcription level of these four genes was downregulated in <em>XNR_0706</em> deletion strain (ΔXNR_0706) and restored by <em>XNR_0706</em> complementation in Δ0706/pIB-<em>0706</em>, demonstrating that XNR_0706 was a positive transcriptional regulator of the genes. With toxic long-chain fatty acids addition in TSB media, deletion of <em>XNR_0706</em> caused significantly poor growth, whereas <em>XNR_0706</em> complementation increased the utilization of additional fatty acids, resulting in restored growth. Fatty acid β-oxidation is one source of acetyl- and malonyl-CoA precursors for polyketides biosynthesis in actinobacteria. Overexpression of <em>XNR_0706</em> in B4/spnNEW, a spinosad heterologous expression strain derived from <em>S. albus</em> B4, increased spinosad yield by 20.6 %. Additionally, supplement of 0.3 g/L fatty acids resulted in a further 42.4 % increase in spinosad yield. Our study reveals a regulatory mechanism in long-chain fatty acids metabolism in <em>S. albus</em> and these insights into the molecular regulation of β-oxidation by XNR_0706 are instrumental for increasing secondary metabolites in actinobacteria.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 218-225"},"PeriodicalIF":4.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142659616","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":"Biosynthesis of the benzylpyrrolidine precursor in anisomycin by a unique ThDP-dependent enzyme","authors":"Yongjian Qiao,&nbsp;Junbo Wang,&nbsp;Dashan Zhang,&nbsp;Xiaoqing Zheng,&nbsp;Baixin Lin,&nbsp;Yongkang Huang,&nbsp;Yulin Liao,&nbsp;Zixin Deng,&nbsp;Lingxin Kong,&nbsp;Delin You","doi":"10.1016/j.synbio.2024.08.006","DOIUrl":"10.1016/j.synbio.2024.08.006","url":null,"abstract":"<div><p>Anisomycin (compound <strong>1</strong>), a multifunctional pyrrolidine antibiotic, primarily inhibits protein biosynthesis by binding to the ribosome. Upon binding to the ribosome, the para-phenol moiety of anisomycin inserts completely into the hydrophobic crevice of the A-site and blocks the access of the incoming aminoacyl-tRNAs, disrupting peptide bond formation. Hence, the para-methoxyphenyl group serves as a starting point for developing novel anisomycin analogs with potent antifungal and insecticidal properties. However, the activation and condensation mechanism of phenylpyruvic acid has not yet been elucidated. In this study, genetic manipulations of <em>aniP</em> and its homologue <em>siAniP</em> confirmed their indispensable role in <strong>1</strong> biosynthesis. Bioinformatics analysis suggested that AniP and siAniP function as transketolase. siAniP was found to catalyzed condensation between 4-hydroxyphenylpyruvic acid (<strong>3</strong>) and glyceraldehyde (GA), initiating pyrrolidine synthesis. siAniP was specific for aromatic keto acids and tolerant of aliphatic and aromatic aldehydes, and was able to catalyze the asymmetric intermolecular condensation of two keto acids, leading to the formation of 24 α-hydroxy ketone. To the best of our knowledge, siAniP is the first TK that catalyzes the transfer of a C2 ketol and symmetrical intermolecular coupling using aromatic keto acids as donor substrates. Structural analysis, docking model construction, and site-directed mutagenesis identified that I220, H275, R322 and W391 were crucial for substrate binding. Moreover, sequence similarity network (SSN)-based genome neighborhood network (GNN) analyses of AniP suggested the widespread occurrence of the AniP-like-mediated reaction in the biosynthesis of <strong>1</strong> and its analogs, particularly in the assembly of benzylpyrrolidine. These findings not only expand the repertoire of TKs but also provide a potent biocatalyst that could be used for the structural innovation of <strong>1</strong> and its derivatives.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 76-85"},"PeriodicalIF":4.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001170/pdfft?md5=a3b2902611aa71c849c7eb7f73b3c4a3&pid=1-s2.0-S2405805X24001170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050440","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}