Metabolic engineering最新文献

{"title":"Systems metabolic engineering of Escherichia coli for high-level branched-chain fatty acid production via dual precursor pathways.","authors":"Mengfan Hu, Cai Feng, Mingjun Li, Wenliang Wang, Yadi Tan, Liqian Zhao, Zhiwei Zhu","doi":"10.1016/j.ymben.2026.102509","DOIUrl":"10.1016/j.ymben.2026.102509","url":null,"abstract":"<p><p>Branched-chain fatty acids (BCFAs), naturally synthesized by Gram-positive bacteria, are promising feedstocks for the production of advanced biofuels. However, efficient BCFA biosynthesis in Gram-negative bacteria such as Escherichia coli remains challenging because of insufficient supply of branched-chain acyl-CoA precursors, poor compatibility of the endogenous fatty acid synthesis pathway with branched-chain substrates, and limited cellular robustness toward non-native fatty acids. In this study, we first engineered an orthogonal isovaleryl-CoA biosynthetic pathway in E. coli and demonstrated its functionality in supporting BCFA production. Importantly, we identified a strong synergistic interaction between the isovaleryl-CoA pathway and the branched-chain α-keto acid dehydrogenase pathway, and thereby established a dual-route strategy for precursor supply. To further enhance BCFA production, we rewired central carbon metabolism by eliminating competing pathways and introducing a non-oxidative glycolysis pathway to increase acetyl-CoA availability while minimizing byproduct formation. We additionally optimized the fatty acid biosynthetic module through expression of a highly active 'TesA (R65C) variant and the transcriptional regulator FadR, and enhanced cellular robustness via introduction of N138H mutation into PcnB and overexpression of the stress resistance associated genes rfaY and yafL. The final engineered strain produced 2.96 g/L BCFAs (approximately 10-fold higher than the previously reported titers), representing 55% of total fatty acids, with a yield of 0.08 g/g glucose. Overall, this work established a dual-precursor supply strategy combined with systems metabolic engineering for BCFA production, providing a foundation for the development of sustainable bioprocesses for advanced branched-chain biofuels.</p>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":"102509"},"PeriodicalIF":7.3,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late-Stage Large Extracellular Vesicles Reprogram CHO Cell Metabolism in a Glutamine-Dependent Mode and Promote Antibody-Productivity to Cell-Growth Tradeoff.","authors":"Hong B Nguyen, Nikola G Malinov, Alekhya Puttagunta, Kelvin H Lee, Eleftherios T Papoutsakis","doi":"10.1016/j.ymben.2026.102567","DOIUrl":"https://doi.org/10.1016/j.ymben.2026.102567","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are mediators of intercellular communication, yet their impact on Chinese Hamster Ovary (CHO) cell physiology and bioprocess performance remains poorly understood. Here, we investigated whether small EVs (sEVs) and large EVs (LgEVs) that accumulate during fed-batch and perfusion cultures modulate CHO cell growth, metabolism, apoptosis, and monoclonal antibody (mAb) production. EVs isolated from early- and late-stage cultures were added to fresh CHO cultures grown with or without glutamine supplementation. Only LgEVs had a significant impact. Late-stage LgEVs markedly altered CHO-cell behavior, reducing cell proliferation, increasing apoptosis under glutamine-limited conditions, and substantially enhancing mAb productivity in a dose-dependent manner. Glutamine supplementation largely alleviated the growth-inhibitory and pro-apoptotic effects of LgEVs while preserving their positive impact on productivity, suggesting that glutamine mitigated the EV-mediated stress without affecting the productivity enhancement. Metabolic analyses revealed increased glucose consumption, a glutamine-dependent shift between glycine and alanine overflow metabolism, and remodeling of amino-acid utilization. Metabolic flux analysis further demonstrated enhanced glycolytic overflow and increased reliance on amino acid-supported anaplerosis. Conversely, selective removal of LgEVs from perfusion medium significantly improved cell expansion without reducing antibody production, supporting an inhibitory role for late-stage LgEVs. These LgEVs were enriched in let-7 family miRNAs and miR-21, consistent with RNAseq analyses demonstrating stress-associated enrichment of these miRNAs in CHO EVs and with functional studies showing that let-7a and miR-21reduce CHO-cell growth. Together, these observations suggest that selective miRNA loading contributes to the growth, metabolic, and productivity phenotypes elicited by late-stage LgEVs. Our findings identify LgEVs in CHO-K1 can act as endogenous regulators of CHO-cell physiology thus deserving attention for optimizing high-density fed-batch and perfusion biomanufacturing processes.</p>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":"102567"},"PeriodicalIF":7.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De novo biosynthesis of the plant-derived aloe-emodin in Aspergillus nidulans via artificial pathway assembly and temporal flux control.","authors":"Nannan Ren, Jing Peng, Nan Zhang, Pinmei Wang, Yike Wang, Qian Jiang, Zhengran Wang, Yihui Chen, Kailai Zhao, Jinzhong Xu","doi":"10.1016/j.ymben.2026.102569","DOIUrl":"10.1016/j.ymben.2026.102569","url":null,"abstract":"<p><p>Traditional botanical extraction of medicinal anthraquinones like aloe-emodin is limited by low yields, long growth cycles, and environmental dependence. Microbial biosynthesis provides a sustainable alternative, but de novo reconstruction of aloe-emodin remains difficult due to unresolved pathway steps and poor metabolic flux distribution in engineered hosts. In this study, we engineered Aspergillus nidulans for the de novo biosynthesis of aloe-emodin via modular assembly of an artificial pathway. We first established an emodin-producing chassis by reconstructing a minimal mdp-derived upstream module and enhancing precursor supply, yielding 86.93 mg/L emodin. Introducing the heterologous cytochrome P450 CYP-H6231 effectively catalyzed the hydroxymethylation of emodin to citreorosein. We then extended the pathway by incorporating the reductive tailoring enzymes MdpK, MdpC, and MdpB to form aloe-emodin. While feeding assays supported a citreorosein-linked route to aloe-emodin, constitutive expression of this downstream module caused unbalanced flux and high accumulation of the competing byproduct chrysophanol. To address this, we applied temporal induction to mdpK. Delaying its expression shifted flux partitioning, significantly reducing chrysophanol formation and improving aloe-emodin selectivity. The final engineered strain achieved 278.06 mg/L citreorosein and 70.97 mg/L aloe-emodin during 1-L fed-batch fermentation. This study establishes a de novo microbial route to aloe-emodin and highlights temporal flux control as a practical strategy for assembling complex plant-derived anthraquinone pathways in fungal cell factories.</p>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":"102569"},"PeriodicalIF":7.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Selective Synthesis of All-trans-crocin I via an in vitro Four-enzyme Cascade System.","authors":"Longlong Gao, Zhijie Shi, Wenjie Xu, Tianyi Xin, Ze Zhou, Xiangdong Pu, Jingyuan Song","doi":"10.1016/j.ymben.2026.102562","DOIUrl":"https://doi.org/10.1016/j.ymben.2026.102562","url":null,"abstract":"<p><strong>Introduction: </strong>All-trans-crocin I (t-crocin I) is the predominant and most extensively studied crocin congener, with antidepressant effects comparable to some first-line antidepressants. However, t-crocin I is still obtained mainly by plant extraction, leading to a high retail price and an unsustainable supply. Despite substantial efforts in heterologous production, most studies generate mixtures of multiple crocin congeners and their cis isomers. Approaches for selective t-crocin I production remain scarce.</p><p><strong>Objectives: </strong>This study aims to establish and optimize an in vitro multi-enzyme cascade for the selective, high-titer production of t-crocin I.</p><p><strong>Methods: </strong>This research proposed an in vitro four-enzyme cascade system comprising the enzymes responsible for crocin biosynthesis in Gardenia jasminoides (GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13). At first, feasibility of the cascade for t-crocin I biosynthesis was verified stepwise using E. coli supernatants and purified proteins. Enzyme activity, reaction conditions, and cofactor usage were then optimized to improve the conversion rate of this system from zeaxanthin to t-crocin I. Finally, to achieve higher titer of t-crocin I, cyclodextrin encapsulation was applied to overcome the low aqueous solubility of zeaxanthin and increase substrate loading.</p><p><strong>Results: </strong>Optimization of reaction conditions and determination of minimum enzyme loadings raised the t-crocin I titer from 5.02 to 8.98 μM at 10 μM zeaxanthin at lower enzyme cost. The GjUGT94E13-to-GjUGT74F8 ratio proved to be the principal determinant of the product distribution: the t-crocin I proportion peaked at 95.68% at a ratio of 1:4, whereas higher ratios diverted the t-crocin I towards a pentaglucosylated crocin derivative. Formulating zeaxanthin as a methyl-β-cyclodextrin inclusion complex raised its aqueous concentration to 1420 μM and allowed a substrate loading of 250 μM, at which the cascade produced 234.0 μM (228.6 mg L^-1) t-crocin I within 3 h, accounting for 96.7% of the total crocins.</p><p><strong>Conclusion: </strong>The in vitro four-enzyme cascade developed here achieves selective, high-titer biosynthesis of t-crocin I directly from a carotenoid substrate, offering a route that preferentially produces t-crocin I while limiting the formation of other crocin congeners.</p>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":"102562"},"PeriodicalIF":7.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orchestrating polyketide synthase-derived aldehyde metabolism for Streptomyces biomanufacturing","authors":"Qingyun Dan,Xina Wang,Yan Chiu,Soonkyu Hwang,Justin J. Baerwald,Yilin Li,Lucas M. Waldburger,Chang Dou,Yiou Rong,Xavier B. Tao,Chenyi Li,Ning Qin,Zhen Liu,Seokjung Cheong,Yan Chen,Jennifer W. Gin,Matthias Schmidt,Rachel E. Sullivan,Tyler W.H. Backman,Christopher J. Petzold,Jay D. Keasling","doi":"10.1016/j.ymben.2026.102570","DOIUrl":"https://doi.org/10.1016/j.ymben.2026.102570","url":null,"abstract":"","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"11 1","pages":"102570"},"PeriodicalIF":8.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"De novo biosynthesis of the polymethoxylated flavones eupatilin and jaceosidin in Saccharomyces cerevisiae\" [Metabol. Eng. 97 (2026), 102502].","authors":"Jingyan Liu, Tianzhen Sun, Zhongjun Liu, Yanli Zou, Yu Liu, Xiaoyu Yao, Hui Wu, Xudong Wang, Fahui Li, Weiguo Song, Yanan Qiao, Xiaozhou Luo","doi":"10.1016/j.ymben.2026.102505","DOIUrl":"10.1016/j.ymben.2026.102505","url":null,"abstract":"","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":"102505"},"PeriodicalIF":7.3,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multisite Cre-lox recombination enables regulatory mechanism elucidation and systematic engineering of echinocandin B biosynthesis in Aspergillus nidulans","authors":"Youchu Ma ,&nbsp;Yue Zhang ,&nbsp;Dongfang Zhang ,&nbsp;Yue Tang ,&nbsp;Wanyu Zhang ,&nbsp;Liyuan Yue ,&nbsp;Wenqing Lou ,&nbsp;Chao Meng ,&nbsp;Yanling Li ,&nbsp;Xiulai Chen ,&nbsp;Fanglong Zhao","doi":"10.1016/j.ymben.2026.01.009","DOIUrl":"10.1016/j.ymben.2026.01.009","url":null,"abstract":"<div><div>Echinocandin B (ECB), a cyclic lipohexapeptide for synthesizing antifungal drugs, is produced by the nonribosomal peptide synthetase gene cluster in <em>Aspergillus nidulans</em>. However, industrial production remains limited by the inefficiency of production capacity, primarily due to the complexity of the biosynthetic pathway and the absence of multi-gene regulatory tools in filamentous fungi. Here, we established an orthogonal Cre-<em>lox</em>-based platform enabling single-site insertion of up to 30 kb and simultaneous dual-site integration of 10 kb DNA fragments in <em>A. nidulans</em>. Through precursor supplementation and targeted gene overexpression, we identified key enzymatic bottlenecks in the precursor biosynthetic pathway, including the oxygenases AniF<em>,</em> AniK<em>,</em> AniG, and the acyl-AMP ligase AniI. Combinatorial overexpression of these genes acted synergistically to increase ECB titers. We further addressed bottlenecks in natural amino acid biosynthesis by overexpressing feedback-resistant mutants of Hom3 (L-Thr pathway) and LeuC (L-Leu pathway). Additionally, we uncovered a temperature-dependent regulation mechanism whereby low temperature (25 °C) concurrently upregulates both the ECB biosynthetic gene cluster and <em>odeA</em> gene, encoding <em>Δ</em>12-oleic acid desaturase, thereby increasing linoleic acid availability for ECB production. Leveraging our multisite DNA-integration platform to rewire expression of these key genes, we increased ECB production to 3.5 ± 0.2 g/L in a 5-L fed-batch bioreactor, a 2.3-fold improvement that represents the highest titer reported in the literature to date. Our orthogonal dual-site integration strategy and the systematic optimization approach provide a valuable framework for metabolic engineering of complex natural products in filamentous fungi.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"95 ","pages":"Pages 15-27"},"PeriodicalIF":6.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating overflow metabolism in heterotrophic cultures of the green alga Chromochloris zofingiensis","authors":"Michelle Meagher ,&nbsp;Dimitrios J. Camacho ,&nbsp;Sean D. Gallaher ,&nbsp;Sabeeha S. Merchant ,&nbsp;Nanette R. Boyle","doi":"10.1016/j.ymben.2026.01.007","DOIUrl":"10.1016/j.ymben.2026.01.007","url":null,"abstract":"<div><div><em>Chromochloris zofingiensis</em> is of interest for its ability to perform a reversible trophic switch in the presence of glucose that is characterized by a shutdown of photosynthesis and an accumulation of energy storage metabolites. Previous work has shown that this trophic switch is accompanied by overflow metabolism and the production of lactate in aerobic conditions. This trophic switch is not observed in nutrient replete media. We utilized isotopically assisted metabolic flux analysis to characterize intracellular flux distributions that are associated with different metabolic phenotypes observed in this organism in different media formulations in light and dark conditions. The results of this analysis showed that low iron cultures have no flux through carbon fixation reactions, and that the carbon flux entering the TCA cycle in these cultures is approximately 40 % lower than that in iron replete cultures grown heterotrophically. This analysis was complemented with transcriptomics data collected for <em>C. zofingiensis</em> grown in iron limited conditions to provide further evidence towards the negative impact of iron limitation on both photosynthetic and respiratory activity. Overflow metabolism allows this alga to compensate for the lower energy production that results from iron limitation. This work highlights how nutrient availability can lead to changes in the metabolism of <em>C. zofingiensis</em>.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"95 ","pages":"Pages 1-14"},"PeriodicalIF":6.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstruction of arginine deiminase pathway sustains a higher-energy state in mammalian cells","authors":"Mauro Torres ,&nbsp;Matthew Reaney ,&nbsp;Kate Meeson ,&nbsp;Devika Kalsi ,&nbsp;Leon P. Pybus ,&nbsp;Alan J. Dickson","doi":"10.1016/j.ymben.2026.02.004","DOIUrl":"10.1016/j.ymben.2026.02.004","url":null,"abstract":"<div><div>ATP is the universal “energy currency” of the cell, and its supply may represent one of several limiting factors influencing the productivity of mammalian cell factories. Here, we present a novel, mitochondria-independent approach to enhance cellular energy metabolism. We engineered Chinese hamster ovary (CHO) cells to express the bacterial arginine deiminase (ADI) pathway along with two arginine transporters. This system enables the direct, cytosolic conversion of arginine to ATP, effectively generating energy without relying solely on the cell's native metabolic machinery. ADI pathway expression was associated with intracellular ATP and concurrent improvements in culture performance across different CHO cell backgrounds. In contrast, cell lines engineered only for enhanced arginine uptake showed no performance gain, consistent with the hypothesis that de-novo ATP generation may contribute to improve productivity. Metabolic profiling revealed that the ADI pathway affects cellular metabolism. We observed a downshift in glycolysis, characterized by decreased glucose consumption and reduced lactate and alanine production, while amino acid and TCA cycle intermediaries remained broadly unchanged. Adenylate measurements and AMPK signalling analysis confirmed a higher energy state (ATP↑, ADP/ATP↓, p-AMPK/AMPK↓) in engineered cells. Supplementing the cell culture medium with arginine or citrulline was associated with further increases in growth and mAb titres in ADI-expressing cells. These results establish the ADI pathway as a powerful and distinct method for enhancing cellular energy. This mitochondria-independent approach highlights a new paradigm for improving the efficiency of industrial bioprocesses.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"95 ","pages":"Pages 63-76"},"PeriodicalIF":6.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146153271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic engineering of Escherichia coli for the high-level production of putrescine","authors":"Yoo-Sung Ko ,&nbsp;Je Woong Kim ,&nbsp;Alisher Nazarbekov ,&nbsp;Gi Bae Kim ,&nbsp;Sang Yup Lee","doi":"10.1016/j.ymben.2026.01.006","DOIUrl":"10.1016/j.ymben.2026.01.006","url":null,"abstract":"<div><div>Putrescine is an important platform chemical used in the manufacture of engineering plastics. To support the development of a sustainable plastics industry, microbial production of putrescine from renewable resources has attracted increasing attention. In this study, we report the development of an engineered <em>Escherichia coli</em> strain capable of efficiently producing putrescine. To overcome the limitation caused by putrescine toxicity, the previously developed XQ52 strain (a W3110-derived putrescine-producing strain) was subjected to adaptive laboratory evolution, resulting in the AXQ52 strain, which produced 61.7 g/L of putrescine in fed-batch fermentation. This titer surpassed the natural tolerance threshold of <em>E. coli</em>. Genome sequencing of the AXQ52 strain revealed mutations that improved cellular fitness under high putrescine concentrations. Further production improvements were achieved by fine-tuning the expression of phosphoenolpyruvate carboxylase gene, introducing a heterologous ornithine acetyltransferase, and disrupting glutamate decarboxylase. The final engineered strain produced 72.7 g/L of putrescine with a yield of 0.25 g/g glucose and a productivity of 1.28 g/L/h, representing the highest microbial putrescine production reported to date from a simple carbon source.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"95 ","pages":"Pages 28-38"},"PeriodicalIF":6.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}