ACS Chemical Biology最新文献

{"title":"Pharmacologic Induction of ERα SUMOylation Disrupts Its Chromatin Binding.","authors":"Lizhen Wang, Ting Han","doi":"10.1021/acschembio.4c00606","DOIUrl":"10.1021/acschembio.4c00606","url":null,"abstract":"<p><p>Estrogen receptor α (ERα)-positive breast cancer patients are typically treated with ERα inhibitors, including selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs). However, the distinct pharmacological properties of various ERα inhibitors remain incompletely understood. In this study, we employed formaldehyde cross-linking followed by ERα immunoprecipitation and mass spectrometry to reveal that fulvestrant, the first FDA-approved SERD, induces the interaction between ERα and SUMO E3 ligases PIAS1 and PIAS2. Biochemical and genomic assays confirmed that fulvestrant induces SUMOylation of ERα, which inhibits ERα's binding to chromatin DNA. In addition, raloxifene (a SERM) and elacestrant (the first FDA-approved oral SERD) were identified as compounds that similarly induce ERα SUMOylation and inhibit its chromatin interaction. Our findings reveal a mechanism by which select ERα inhibitors disrupt ERα function through SUMOylation, offering insights for the development of next-generation ERα-targeted therapies.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"2383-2392"},"PeriodicalIF":3.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453205","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":"Discovery of a Compound That Inhibits IRE1α S-Nitrosylation and Preserves the Endoplasmic Reticulum Stress Response under Nitrosative Stress","authors":"Haruna Kurogi,&nbsp;Nobumasa Takasugi,&nbsp;Sho Kubota,&nbsp;Ashutosh Kumar,&nbsp;Takehiro Suzuki,&nbsp;Naoshi Dohmae,&nbsp;Daisuke Sawada,&nbsp;Kam Y.J. Zhang and Takashi Uehara*,&nbsp;","doi":"10.1021/acschembio.4c0040310.1021/acschembio.4c00403","DOIUrl":"https://doi.org/10.1021/acschembio.4c00403https://doi.org/10.1021/acschembio.4c00403","url":null,"abstract":"<p >Inositol-requiring enzyme 1α (IRE1α) is a sensor of endoplasmic reticulum (ER) stress and drives ER stress response pathways. Activated IRE1α exhibits RNase activity and cleaves mRNA encoding X-box binding protein 1, a transcription factor that induces the expression of genes that maintain ER proteostasis for cell survival. Previously, we showed that IRE1α undergoes <i>S</i>-nitrosylation, a post-translational modification induced by nitric oxide (NO), resulting in reduced RNase activity. Therefore, <i>S</i>-nitrosylation of IRE1α compromises the response to ER stress, making cells more vulnerable. We conducted virtual screening and cell-based validation experiments to identify compounds that inhibit the <i>S</i>-nitrosylation of IRE1α by targeting nitrosylated cysteine residues. We ultimately identified a compound (1ACTA) that selectively inhibits the <i>S</i>-nitrosylation of IRE1α and prevents the NO-induced reduction of RNase activity. Furthermore, 1ACTA reduces the rate of NO-induced cell death. Our research identified <i>S</i>-nitrosylation as a novel target for drug development for IRE1α and provides a suitable screening strategy.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 12","pages":"2429–2437 2429–2437"},"PeriodicalIF":3.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862481","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":"Small Molecule Modulator of the mTORC2 Pathway Discovered from a DEL Library Designed to Bind to Pleckstrin Homology Domains","authors":"Arthur Gonse,&nbsp;Jelena Gajić,&nbsp;Jean-Pierre Daguer,&nbsp;Sofia Barluenga,&nbsp;Robbie Loewith* and Nicolas Winssinger*,&nbsp;","doi":"10.1021/acschembio.4c0059710.1021/acschembio.4c00597","DOIUrl":"https://doi.org/10.1021/acschembio.4c00597https://doi.org/10.1021/acschembio.4c00597","url":null,"abstract":"<p >Pleckstrin homology (PH) domains are structural motifs critical for cellular processes, such as signal transduction and cytoskeletal organization. Due to their involvement in various diseases, PH domains are promising therapeutic targets, yet their highly charged and hydrophobic binding sites are not ideal for traditional small drugs. In this study, we designed a DNA-encoded library (DEL) mimicking phospholipids to identify novel modulators targeting PH domains with uncharted chemical properties. Screening against several PH domains led to the discovery of 2DII, a small molecule that selectively binds to mSin1^PH. This compound can modulate mTORC2 activity by impairing mTORC2’s membrane interactions, resulting in reduced AKT1 phosphorylation. A micromapping via Dexter energy transfer based on 2DII bearing an iridium catalyst (2DII-Ir), along with a biotin-diazirine small molecule was used for target identification by proteomics, which confirmed mSin1 as the primary intracellular target of 2DII, demonstrating its potential for selective mTORC2 pathway modulation. These findings introduce a novel strategy for targeting PH domains and provide a foundation for the development of therapeutic interventions that modulate PH-domain-dependent signaling pathways.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 12","pages":"2502–2514 2502–2514"},"PeriodicalIF":3.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858752","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":"Photoresponsive Adenosine Derivatives for the Optical Control of Adenosine A2A Receptors in Living Cells","authors":"Harufumi Suzuki,&nbsp;Tomohiro Doura*,&nbsp;Yuya Matsuba,&nbsp;Yuma Matsuoka,&nbsp;Tsuyoshi Araya,&nbsp;Hidetsugu Asada,&nbsp;So Iwata and Shigeki Kiyonaka*,&nbsp;","doi":"10.1021/acschembio.4c0058310.1021/acschembio.4c00583","DOIUrl":"https://doi.org/10.1021/acschembio.4c00583https://doi.org/10.1021/acschembio.4c00583","url":null,"abstract":"<p >The use of photoresponsive ligands to optically control proteins of interest, known as photopharmacology, is a powerful technique for elucidating cellular function in living cells and animals with a high spatiotemporal resolution. The adenosine A_2A receptor (A_2AR) is a G protein-coupled receptor that is expressed in various tissues; its dysregulation is implicated in severe diseases such as insomnia and Parkinson’s disease. A detailed elucidation of the physiological function of A_2AR is, therefore, highly desirable. In the present study, we developed two photoswitchable ligands, photoAd(blue) and photoAd(vio), that target A_2AR. Using photoAd(vio), we successfully demonstrated the selective activation of A_2AR in living cells by violet-light irradiation with high spatiotemporal resolution.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 12","pages":"2494–2501 2494–2501"},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Substrate Selectivity of the Fimsbactin Biosynthetic Adenylation Domain, FbsH","authors":"Syed Fardin Ahmed,&nbsp;Adam Balutowski,&nbsp;Jinping Yang,&nbsp;Timothy A. Wencewicz* and Andrew M. Gulick*,&nbsp;","doi":"10.1021/acschembio.4c0051210.1021/acschembio.4c00512","DOIUrl":"https://doi.org/10.1021/acschembio.4c00512https://doi.org/10.1021/acschembio.4c00512","url":null,"abstract":"<p >Nonribosomal peptide synthetases (NRPSs) produce diverse natural products including siderophores, chelating agents that many pathogenic bacteria produce to survive in low iron conditions. Engineering NRPSs to produce diverse siderophore analogs could lead to the generation of novel antibiotics and imaging agents that take advantage of this unique iron uptake system in bacteria. The highly pathogenic and antibiotic-resistant bacteria <i>Acinetobacter baumannii</i> produces fimsbactin, an unusual branched siderophore with iron-binding catechol groups bound to a serine or threonine side chain. To explore the substrate promiscuity of the assembly line enzymes, we report a structure-guided investigation of the stand-alone aryl adenylation enzyme FbsH. We report structures bound to its native substrate 2,3-dihydroxybenzoic acid (DHB) as well as an inhibitor that mimics the adenylate intermediate. We produced enzyme variants with an expanded binding pocket that are more tolerant for analogs containing a DHB C4 modification. Wild-type and mutant enzymes were then used in an in vitro reconstitution analysis to assess the production of analogs of the final product as well as several early stage intermediates. This analysis shows that some altered substrates progress down the fimsbactin assembly line to the downstream domains. However, analogs from alternate building blocks are produced at lower levels, indicating that selectivity exists in the downstream catalytic domains. These findings expand the substrate scope of producing condensation products between serine and aryl acids and identify the bottlenecks for chemoenzymatic production of fimsbactin analogs.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 12","pages":"2451–2461 2451–2461"},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP","authors":"Fumei Zhong,&nbsp;Yu Zhou,&nbsp;Mingqing Liu,&nbsp;Lei Wang,&nbsp;Fudong Li,&nbsp;Jiahai Zhang,&nbsp;Zhiyong Han,&nbsp;Yunyu Shi*,&nbsp;Jia Gao* and Ke Ruan*,&nbsp;","doi":"10.1021/acschembio.4c0054110.1021/acschembio.4c00541","DOIUrl":"https://doi.org/10.1021/acschembio.4c00541https://doi.org/10.1021/acschembio.4c00541","url":null,"abstract":"<p >The E3 ligase HOIP is vital for the NF-κB pathway and is implicated in cancer and immunity. However, it remains challenging to achieve high selectivity by directly targeting the conserved catalytic RBR domain of HOIP. Herein, we identified four low-molecular-weight compounds that bind to an uncharacterized pocket of the HOIP PUB domain (HOIP^PUB). The complex structure facilitated the discovery of the first single-digit micromolar ligand of HOIP^PUB, tolfenamic acid, which exhibited over 30-fold selectivity due to the low sequence identity of the uncharacterized pocket of HOIP^PUB. Although tolfenamic acid did not block the substrate recognition and linear ubiquitination activity of HOIP, a ligand of the uncharacterized PUB pocket of HOIP (LUPH), by chemical linking pomalidomide with tolfenamic acid, degraded HOIP, reduced NEMO ubiquitination and p65 phosphorylation, and eventually inhibited NF-κB activation and breast cancer cell proliferation. Our work proposes an alternative strategy to target the nonfunctional pocket of the PUB domain with high sequence diversity to promote HOIP degradation, rather than targeting the conserved RBR domain to block the catalytic function of HOIP.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 12","pages":"2469–2476 2469–2476"},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailored Bisacylphosphane Oxides for Precise Induction of Oxidative Stress-Mediated Cell Death in Biological Systems.","authors":"Karim Almahayni, Jana Bachir Salvador, Riccardo Conti, Anna Widera, Malte Spiekermann, Daniel Wehner, Hansjörg Grützmacher, Leonhard Möckl","doi":"10.1021/acschembio.4c00399","DOIUrl":"https://doi.org/10.1021/acschembio.4c00399","url":null,"abstract":"<p><p>Precise cell elimination within intricate cellular populations is hampered by issues arising from the multifaceted biological properties of cells and the expansive reactivity of chemical agents. Current chemical platforms are often limited by their complexity, toxicity, and poor physical/chemical properties. Here, we report on the synthesis of a structurally versatile library of chemically tunable bisacylphosphane oxides (BAPOs), which harnesses the spatiotemporal precision of light delivery, thereby establishing a universal strategy for on-demand, precise cellular ablation <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Redundancy and Dual Function of a Hypothetical Protein in the Biosynthesis of Eunicellane-Type Diterpenoids","authors":"Ayesha Ahmed Chaudhri,&nbsp;Yuya Kakumu,&nbsp;Sirinthra Thiengmag,&nbsp;Jack Chun-Ting Liu,&nbsp;Geng-Min Lin,&nbsp;Suhan Durusu,&nbsp;Friederike Biermann,&nbsp;Miriam Boeck,&nbsp;Christopher A. Voigt,&nbsp;Jon Clardy,&nbsp;Reiko Ueoka,&nbsp;Allison S. Walker and Eric J. N. Helfrich*,&nbsp;","doi":"10.1021/acschembio.4c0041310.1021/acschembio.4c00413","DOIUrl":"https://doi.org/10.1021/acschembio.4c00413https://doi.org/10.1021/acschembio.4c00413","url":null,"abstract":"<p >Many complex terpenoids, predominantly isolated from plants and fungi, show drug-like physicochemical properties. Recent advances in genome mining revealed actinobacteria as an almost untouched treasure trove of terpene biosynthetic gene clusters (BGCs). In this study, we characterized a terpene BGC with an unusual architecture. The selected BGC includes, among others, genes encoding a terpene cyclase fused to a truncated reductase domain and a cytochrome P450 monooxygenase (P450) that is split over three gene fragments. Functional characterization of the BGC in a heterologous host led to the identification of several new members of the <i>trans</i>-eunicellane family of diterpenoids, the euthailols, that feature unique oxidation patterns. A combination of bioinformatic analyses, structural modeling studies, and heterologous expression revealed a dual function of the pathway-encoded hypothetical protein that acts as an isomerase and an oxygenase. Moreover, in the absence of other tailoring enzymes, a P450 hydroxylates the eunicellane scaffold at a position that is not modified in other eunicellanes. Surprisingly, both the modifications installed by the hypothetical protein and one of the P450s exhibit partial redundancy. Bioactivity assays revealed that some of the euthailols show growth inhibitory properties against Gram-negative ESKAPE pathogens. The characterization of the euthailol BGC in this study provides unprecedented insights into the partial functional redundancy of tailoring enzymes in complex diterpenoid biosynthesis and highlights hypothetical proteins as an important and largely overlooked family of tailoring enzymes involved in the maturation of complex terpenoids.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2314–2322 2314–2322"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142641098","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":"Bioorthogonal Monomycolate of Trehalose Disclosed the O-Mycoloylation of Mycoloyltransferases and Other Cell Envelope Proteins in C. glutamicum","authors":"Cécile Labarre,&nbsp;Yijie Zhang,&nbsp;Emilie Lesur,&nbsp;Marie Ley,&nbsp;Laila Sago,&nbsp;Christiane Dietrich,&nbsp;Célia de Sousa-d’Auria,&nbsp;Florence Constantinesco-Becker,&nbsp;Aurélie Baron,&nbsp;Gilles Doisneau,&nbsp;Dominique Urban,&nbsp;Guillaume Chevreux,&nbsp;Dominique Guianvarc’h,&nbsp;Yann Bourdreux* and Nicolas Bayan*,&nbsp;","doi":"10.1021/acschembio.4c0050210.1021/acschembio.4c00502","DOIUrl":"https://doi.org/10.1021/acschembio.4c00502https://doi.org/10.1021/acschembio.4c00502","url":null,"abstract":"<p >Protein mycoloylation is a recently identified unusual post-translational modification (PTM) exclusively observed in Mycobacteriales, an order of bacteria that includes several human pathogens. These bacteria possess a distinctive outer membrane, known as the mycomembrane, composed of very long-chain fatty acids called mycolic acids. It has been demonstrated that a few mycomembrane proteins undergo covalent modification with mycolic acids in the model organism <i>Corynebacterium glutamicum</i> through the action of mycoloyltransferase MytC. This PTM represents the first example of protein <i>O</i>-acylation in prokaryotes and also the first example of protein modification by mycolic acid. Many questions about the specificity of protein <i>O</i>-mycoloylation remain crucial for understanding its evolutionary significance in Mycobacteriales and its role in cell physiology. We have developed the first bioorthogonal mycolate donor featuring the natural mycolic acid pattern, enabling direct, unambiguous transfer of the lipid moiety to its acceptors and efficient metabolic labeling and enrichment of MytC protein substrates. Mass spectrometry analysis of the labeled proteins and comparative proteomic analysis of the cell envelope proteome between wild-type and Δ<i>mytC</i> strains identified an unbiased list of 21 proteins likely mycoloylated in the cell. The robustness of our approach is demonstrated by the successful biological validation of mycoloylation in 6 candidate proteins within wild-type cells, revealing the characteristic profile of proteins modified with natural mycolates. These findings provide interesting insights into the significance of this new lipidation pathway and pave the way for understanding their function, especially concerning the mycoloyltransferase family that includes the essential Antigen85 enzymes in Mycobacteria.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2359–2371 2359–2371"},"PeriodicalIF":3.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Steps of the Biosynthesis of the Anticancer Antibiotic Pleurotin","authors":"Jack A. Weaver,&nbsp;Duha Alkhder,&nbsp;Panward Prasongpholchai,&nbsp;Michaël D. Tadesse,&nbsp;Emmanuel L. de los Santos,&nbsp;Lijiang Song,&nbsp;Christophe Corre and Fabrizio Alberti*,&nbsp;","doi":"10.1021/acschembio.4c0059910.1021/acschembio.4c00599","DOIUrl":"https://doi.org/10.1021/acschembio.4c00599https://doi.org/10.1021/acschembio.4c00599","url":null,"abstract":"<p >Pleurotin is a meroterpenoid specialized metabolite made by the fungus <i>Hohenbuehelia grisea</i>, and it is a lead anticancer molecule due to its irreversible inhibition of the thioredoxin-thioredoxin reductase system. Total synthesis of pleurotin has been achieved, including through a stereoselective route; however, its biosynthesis has not been characterized. In this study, we used isotope-labeled precursor feeding to show that the nonterpenoid quinone ring of pleurotin and its congeners is derived from phenylalanine. We sequenced the genome of <i>H. grisea</i> and used comparative transcriptomics to identify putative genes involved in pleurotin biosynthesis. We heterologously expressed a UbiA-like prenyltransferase from <i>H. grisea</i> that led to the accumulation of the first predicted pleurotin biosynthetic intermediate, 3-farnesyl-4-hydroxybenzoic acid. This work sets the foundation to fully elucidate the biosynthesis of pleurotin and its congeners, with long-term potential to optimize their production for therapeutic use and engineer the pathway toward the biosynthesis of valuable analogues.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"19 11","pages":"2284–2290 2284–2290"},"PeriodicalIF":3.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640928","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}