{"title":"Improvement of alka(e)ne production in Escherichia coli by the 3′-UTR engineering of acyl-ACP reductase","authors":"Jiahu Han, Takuya Matsumoto, Ryosuke Yamada, Hiroyasu Ogino","doi":"10.1016/j.bej.2025.109725","DOIUrl":"10.1016/j.bej.2025.109725","url":null,"abstract":"<div><div>The sustainable and efficient production of biofuels has generated considerable interest in the microbial synthesis of alka(e)nes, which are promising alternatives to fossil fuels. Acyl-ACP reductase (AAR) is a critical enzyme in the alka(e)ne biosynthetic pathway, and its poor solubility in <em>Escherichia coli</em> is a major bottleneck during the optimization of production yields. The approaches for enhancing protein solubility typically include the fusion of solubility tags at the N- or C-termini of target proteins, which can sometimes interfere with protein function or stability. The present study developed a novel strategy that leverages the regulatory potential of 3′-untranslated regions (3′-UTRs) by integrating the sequence coding thioredoxin (Trx), small ubiquitin-like modifier (SUMO), maltose-binding protein (MBP), or N-utilization substance protein A (NusA), into the 3′-UTR of the <em>AAR</em> gene. The strategy aimed to enhance the stability of AAR mRNA for improving the solubility and expression of AAR without altering its primary structure. The findings revealed that this strategy significantly enhanced the solubility and expression levels of AAR in <em>Escherichia coli</em>, which markedly increased alka(e)ne production. This method has potential widespread applications in metabolic engineering and synthetic biology. The study paves the way for the development of more efficient strategies aimed at producing biofuels, and highlights the untapped potential of the 3′-UTR engineering strategy.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109725"},"PeriodicalIF":3.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin F. Luna , Federico M. Mione , Lucas Kaspersetz , Peter Neubauer , Ernesto C. Martinez , M. Nicolas Cruz Bournazou
{"title":"Automated regression of bioreactor models using a Bayesian approach for parallel cultivations in robotic platforms","authors":"Martin F. Luna , Federico M. Mione , Lucas Kaspersetz , Peter Neubauer , Ernesto C. Martinez , M. Nicolas Cruz Bournazou","doi":"10.1016/j.bej.2025.109729","DOIUrl":"10.1016/j.bej.2025.109729","url":null,"abstract":"<div><div>Mathematical models of bioreactors are powerful tools that aid in the analysis and prediction of process operation. However, the complex behavior of microorganisms makes modelling of biological processes a particularly challenging task, especially in the early developmental stages when data and knowledge are scarce. As a result, bioreactor models may perform poorly due to structural errors or high uncertainty in their parameterization. Here, we present a method for automated dynamic model regression based on a Bayesian approach that can be applied in the operation of laboratory robotic platforms to perform both parameter estimation and state predictions for a given experimental design. Starting with wide distributions over parameters (prior knowledge), the model is updated as new data is generated and is then used to predict the evolution of the experiment. The proposed method is tested with data from several parallel cultivations from a 24 mini-bioreactors platform containing an <em>Escherichia coli</em> strain operating in fed-batch mode. The results highlight both the versatility of the approach to estimate parameter distribution as well as to predict the state evolution.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109729"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Girish H. Rajacharya , Jashwant Kumar , Jaya A. Gupta , Anurag S. Rathore
{"title":"Impact of stringent stress response and amino acid supplementation on recombinant protein production in Escherichia coli","authors":"Girish H. Rajacharya , Jashwant Kumar , Jaya A. Gupta , Anurag S. Rathore","doi":"10.1016/j.bej.2025.109727","DOIUrl":"10.1016/j.bej.2025.109727","url":null,"abstract":"<div><div>The metabolic response of <em>Escherichia coli</em> BL21 DE3 strains upon amino acid supplementation and stringent stress was examined to assess its effects on growth, protein production, metabolic efficiency, and cellular stress. In the absence of amino acids, <em>E. coli</em> prioritized amino acid synthesis, essential for recombinant protein production. Supplementation led to faster growth, higher cell densities, and reduced acetate accumulation, indicating improved metabolic balance. Proteomic analysis revealed notable changes in protein abundance during the early log and post-induction mid-log phases, with supplemented cultures showing enhanced metabolic capacity and reduced stress levels. Gene expression analysis demonstrated that amino acid availability downregulated stress response genes and upregulated genes associated with nutrient uptake and metabolism, boosting growth and productivity. Specifically, genes <em>lldR</em>, <em>ydgR</em>, <em>tppB</em>, and <em>yhhN</em> were upregulated, while <em>adiA</em> and <em>ydeI</em> were downregulated, reflecting better metabolic conditions. Stringent response analysis showed elevated (p)ppGpp levels and increased activities of SpoT and RelA without supplementation, indicative of nutrient stress. Supplementation lowered these stress markers, fostering a favourable metabolic state. The study underscores the importance of amino acid supplementation for optimizing biomass production and recombinant protein yields, offering insights into <em>E. coli</em> physiology and strategies for metabolic engineering.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109727"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Voltage application and biomass retention increased biogas production in a combined microbial electrolysis cell and anaerobic digestion system treating chicken manure","authors":"Kenan Dalkılıç , Elvin Aghayev , Eda Sinoplu","doi":"10.1016/j.bej.2025.109728","DOIUrl":"10.1016/j.bej.2025.109728","url":null,"abstract":"<div><div>This study investigates the effect of the voltage application and biomass retention on the biogas production performance of a combined microbial electrolysis cell and anaerobic digestion (MEC+AD) reactor operated at different organic loading rates (OLR). The chicken manure (CM) with a content of 6 % VS was fed to the reactors as substrate at various hydraulic retention times (HRT) ranging from 3 to 20 days. It was observed that the conventional anaerobic digestion (AD) reactor collapsed due to the overloading at the HRT of 5 days. On the other hand, due to the voltage application and biomass retention on the electrodes of the combined reactors, (MEC+AD)<sub>C</sub> without a voltage application and (MEC+AD)<sub>0.3</sub> with a voltage application of 0.3 V presented the highest methane production of 1.98 ± 0.19 and 2.37 ± 0.32 L/L<sub>R</sub>/d, respectively. Organic removal rates of the combined reactors were similar to each other; however, in terms of biogas production, (MEC+AD)<sub>0.3</sub> presented superior performance at all sets due to the voltage application and microbial community on the electrodes. <em>Methanosarcina</em> had a dominance of 5 % at the cathode of (MEC+AD)<sub>0.3</sub> at the genus level, which affected the results. The highest methane yield obtained in this study was 373 ± 72 mL CH<sub>4</sub>/g VS at (MEC+AD)<sub>0.3,</sub> which was 30 % higher than that of (MEC+AD)<sub>C</sub> due to the voltage application and the genus <em>Methanosarcina</em> on the cathode.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109728"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinxin Chen , Xiaohan Jiang , Bo Zhang , Zhiqiang Liu , Yuguo Zheng
{"title":"Rerouting of phytosterol degradation pathways in targeted high-yield and high-purity 9α-hydroxyandrost-4-ene-3,17-dione microbial biotransformation","authors":"Xinxin Chen , Xiaohan Jiang , Bo Zhang , Zhiqiang Liu , Yuguo Zheng","doi":"10.1016/j.bej.2025.109723","DOIUrl":"10.1016/j.bej.2025.109723","url":null,"abstract":"<div><div>9α-Hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a representative precursor in steroid drug synthesis. However, during the 9-OHAD production from phytosterol in <em>Mycolicibacterium neoaurum</em> (<em>M. neoaurum</em>), the current manufacturing processes suffer from low productivity and purity due to the generation of a variety of by-products. In this study, we genetically modified the phytosterol catabolism <em>in M. neoaurum</em> and achieved 13.4 g/L and 91.1 % molar yield of 9-OHAD with no detectable by-products at a high phytosterol concentration of 20 g/L in shake flask. It was achieved by inactivating <em>Opccr</em>, <em>SalA</em>, <em>TeB</em>, and overexpressing <em>KshA1</em> and <em>ChsH1–2</em> to eliminate the production of 20-hydroxymethyl-9,21-dihydroxy-20-methyl-pregna-4-en-3-one (9-OH-4-HBC), 4-androstene-3,17-dione (4-AD) and 3-oxo-4-pregnene-9-OH-20-carboxylic methyl ester (9-OH-3-OPCM) as well as overcoming the production limitations of 9-OHAD. Notably, when scaled up in a 5 L bioreactor with 45 g/L phytosterol concentration, the modified <em>M. neoaurum</em> achieved 24.5 g/L and 74.5 % molar conversion of 9-OHAD by using soybean oil and (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) as a co-solvent and antifoam agent. Therefore, our findings demonstrate a method to improve the efficiency and purity of 9-OHAD biosynthesis in <em>M. neoaurum</em>.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109723"},"PeriodicalIF":3.7,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kunming Fu , Zirui Li , Huifang Wang , Hui Li , Xueying Su
{"title":"Effects of aeration conditions on nitrogen removal performance and N2O emissions in a biofilm CANON reactor","authors":"Kunming Fu , Zirui Li , Huifang Wang , Hui Li , Xueying Su","doi":"10.1016/j.bej.2025.109724","DOIUrl":"10.1016/j.bej.2025.109724","url":null,"abstract":"<div><div>The complete autotrophic nitrogen removal over nitrite (CANON) process offers significant nitrogen removal benefits, but N<sub>2</sub>O emissions remain a concern. This study used a sequencing batch biofilm reactor (SBBR) to examine how different aeration conditions (aeration rates and strategies) affect N2O emissions during CANON. In the experiment, N<sub>2</sub>O emissions were collected and calculated every 30 min, with nitrogen removal efficiency (NRE) maintained between 81 % and 92 %. The results showed that under continuous aeration conditions, as the aeration rate increased from 1 m<sup>3</sup>·(m<sup>3</sup>·h)<sup>−1</sup> to 8 m<sup>3</sup>·(m<sup>3</sup>·h)<sup>−1</sup>, N<sub>2</sub>O emissions significantly increased from 2.99 mg to 20.23 mg, and the emission proportion increased from 1.53 % to 9.74 %. Under intermittent aeration conditions, when the aeration rate was maintained at 8 m<sup>3</sup>·(m<sup>3</sup>·h)<sup>−1</sup> and the initial aerobic phase was shortened by 30 min, the system rapidly shifted from aerobic to anaerobic conditions, reducing N<sub>2</sub>O emissions from 16.16 mg to 12.69 mg, with the emission proportion dropping from 7.94 % to 6.1 %. At this point, the concentration of NO<sub>2</sub><sup>-</sup>-N decreased from 27.77 mg·L<sup>−1</sup> to 18 mg·L<sup>−1</sup>. The study suggests that the aeration rate influences N<sub>2</sub>O generation by regulating dissolved oxygen (DO) concentration and NO<sub>2</sub><sup>-</sup>-N accumulation, and affects its release through the gas stripping effect. Appropriately shortening the duration of both the aerobic and anaerobic phases can effectively reduce N<sub>2</sub>O emissions.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109724"},"PeriodicalIF":3.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zwonaka Mapholi, George Mbella Teke, Neill Jurgens Goosen
{"title":"An investigation of kinetics and mass transfer parameters during ultrasound-assisted extraction of fucoidan from the brown seaweed Ecklonia maxima","authors":"Zwonaka Mapholi, George Mbella Teke, Neill Jurgens Goosen","doi":"10.1016/j.bej.2025.109717","DOIUrl":"10.1016/j.bej.2025.109717","url":null,"abstract":"<div><div>Fucoidan, a bioactive sulfated polysaccharide from brown seaweed, holds significant industrial potential. This study explores ultrasound-assisted extraction (UAE) using a batch recirculation flow cell for fucoidan extraction. The impacts of ultrasound amplitude (0 – 190 μm), temperature (25 – 85 ℃) and pH (3 – 11) were evaluated on mass transfer parameters – effective diffusivity, mass transfer coefficient, initial extraction rate, and the sulfates equilibrium concentration. These parameters were modelled using Fick’s second law, the mass transfer model and the Peleg model, all of which demonstrated good agreement with experimental data (R<sup>2</sup> > 0.89). UAE (at 190 μm) significantly enhances extraction kinetics, increasing effective diffusivity from 0.863 to 3.46 × 10<sup>−12</sup> m<sup>2</sup>·s<sup>−1</sup> and mass transfer coefficient from 0.451 to 1.84 × 10<sup>−6</sup> m·s<sup>−1</sup> compared to no ultrasound. Higher temperatures and higher amplitudes enhance the mass transfer rates, while pH beyond 5 reduces these rates due to alginates co-extraction, but increased sulfates equilibrium concentration, suggesting benefits for maximising final yields. UAE of fucoidan is an internal diffusion-limited process (Biot numbers > 50).</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109717"},"PeriodicalIF":3.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rucha S. Patil, Drashti P. Trivedi, Anurag S. Rathore
{"title":"Amino acid supplementation to achieve enhanced production of a fab fragment in Escherichia coli: rHu ranibizumab as a case study","authors":"Rucha S. Patil, Drashti P. Trivedi, Anurag S. Rathore","doi":"10.1016/j.bej.2025.109718","DOIUrl":"10.1016/j.bej.2025.109718","url":null,"abstract":"<div><div>Microbial host systems, specifically <em>E. coli</em>-based, are widely used hosts for the production of recombinant proteins and biotherapeutics. Overproduction of heterologous protein often causes excessive consumption of ATPs and other precursors, especially amino acids, and this can disrupt cell metabolism, thereby resulting in reduced cell growth and protein production. In this study, we demonstrate that supplementation of amino acids can reduce metabolic burden and thereby improve the biomass and protein yield. Ranibizumab, a fab fragment biotherapeutic, has been taken as a case study. Plackett-Burman Design of Experiments (DOE) based screening of all 20 amino acids was performed first to identify significant amino acids. Further, to confirm the finding of the screening study, consumption of amino acids was monitored and based on the pattern, the required amino acids were supplemented. This targeted amino acid supplementation resulted in a significant increase in biomass (28 % increase in dry cell weight), protein titre (40 % increase in g protein per g IBs), specific growth rate (by 23 %), and substrate uptake (by 37 %). The results demonstrate that optimal amino acid supplementation enhances process productivity.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109718"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiayan Du , Youtong Bao , Jingyuan Zhu , Xueqing Pang , Depeng Ren , Xinjian Yin , Pingping Zhou
{"title":"Engineering of β-carotene hydroxylase for enhanced astaxanthin production in Saccharomyces cerevisiae","authors":"Jiayan Du , Youtong Bao , Jingyuan Zhu , Xueqing Pang , Depeng Ren , Xinjian Yin , Pingping Zhou","doi":"10.1016/j.bej.2025.109722","DOIUrl":"10.1016/j.bej.2025.109722","url":null,"abstract":"<div><div>Astaxanthin, a potent antioxidant widely applied in health supplements, cosmetics, and animal feed, faces production challenges in microbial synthesis due to inefficient β-carotene hydroxylase activity. This study identified rate-limiting enzymes and demonstrated that the expressing phytoene desaturase BtCrtI from <em>Blakeslea trispora</em> in <em>Saccharomyces cerevisiae</em> increased β-carotene production 2.8-fold compared to XdCrtI from <em>Xanthophyllomyces dendrorhous</em>. Integrating of XdCrtYB, BtCrtI, CrtE03M, and tHMG1 achieved 208.7 mg/L β-carotene. However, introducing β-carotene ketolase and β-carotene hydroxylase into this strain unexpectedly increased lycopene accumulation, likely due to feedback inhibition by the product and enzyme imbalance. To address this, we utilized a moderate β-carotene producer YJYast-02 for astaxanthin production. Truncating the N-terminal 39 amino acids of β-carotene hydroxylase from <em>Haematococcus pluvialis</em> improved astaxanthin titer by 37.7 %. Rational engineering of the hydrophobicity of the substrate-binding pocket in β-carotene hydroxylase, specifically through mutations such as N183A, C191A and T213A, further increased astaxanthin titer by 15.8 %, 30.5 %, 36.8 %, respectively. The final engineered strain, YJYast-03(t5t39<sup>T213A</sup>), expressing t5OBKTM30 and t39OcrtZM1<sup>T213A</sup>, achieved 26.0 mg/L (3.6 mg/g DCW) astaxanthin. This work pioneers the use of molecular docking for engineering β-carotene hydroxylase, offering potential to significantly enhance catalytic activity and optimize astaxanthin biosynthesis in yeast.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109722"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuexi Fang, Xinhua Tang, Shiyang Zhang, Jialong Xiao, Xingyuan Li
{"title":"Short-circuited microbial fuel cell enhanced denitrification in pyrite packed-bed bioreactor","authors":"Xuexi Fang, Xinhua Tang, Shiyang Zhang, Jialong Xiao, Xingyuan Li","doi":"10.1016/j.bej.2025.109720","DOIUrl":"10.1016/j.bej.2025.109720","url":null,"abstract":"<div><div>Pyrite autotrophic denitrification (PAD) faces challenges in electron utilization efficiency for treating low C/N wastewater. Here, we proposed a short-circuited microbial fuel cell (SMFC) integrated with a pyrite-packed bioreactor to overcome these limitations. Unlike conventional MFCs requiring external circuits, the SMFC employed an internal short-circuited design (direct anode-cathode connection via titanium wires), eliminating external power supply while enabling spontaneous electron transfer from the anode to the cathode. This configuration enhanced total nitrogen (TN) removal by 7.93 % compared to standalone PAD, with effluent NO₂⁻-N stably below 1 mg/L. High-throughput sequencing revealed that <em>Phycisphaerae</em> (27 % abundance on the cathode) was a key genus, utilizing bioelectrons from the SMFC to drive complete nitrite reduction via dissimilatory Onr genes. The SMFC-PAD system achieved a 28.4 % increase in electron utilization efficiency by optimizing electron flux between pyrite oxidation (anode) and denitrification (cathode), overcoming intermediate accumulation of nitrite in traditional PAD. This work demonstrated a cost-effective strategy for denitrification by leveraging spatial electron regulation and microbial-electrochemical synergies.</div></div>","PeriodicalId":8766,"journal":{"name":"Biochemical Engineering Journal","volume":"219 ","pages":"Article 109720"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}