Metabolic engineering最新文献

Evolution-guided tolerance engineering of Pseudomonas putida KT2440 for production of the aviation fuel precursor isoprenol. 进化引导恶臭假单胞菌KT2440生产航空燃料前体异戊二醇的耐受性工程。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-19 DOI: 10.1016/j.ymben.2025.05.007

Hyun Gyu Lim, Aparajitha Srinivasan, Russel Menchavez, Ian S Yunus, Myung Hyun Noh, Megan White, Yan Chen, Jennifer W Gin, Bernhard O Palsson, Taek Soon Lee, Christopher J Petzold, Thomas Eng, Aindrila Mukhopadhyay, Adam M Feist

{"title":"Evolution-guided tolerance engineering of Pseudomonas putida KT2440 for production of the aviation fuel precursor isoprenol.","authors":"Hyun Gyu Lim, Aparajitha Srinivasan, Russel Menchavez, Ian S Yunus, Myung Hyun Noh, Megan White, Yan Chen, Jennifer W Gin, Bernhard O Palsson, Taek Soon Lee, Christopher J Petzold, Thomas Eng, Aindrila Mukhopadhyay, Adam M Feist","doi":"10.1016/j.ymben.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.ymben.2025.05.007","url":null,"abstract":"<p><p>Isoprenol (3-methyl-3-buten-1-ol) is a precursor to aviation fuels and other commodity chemicals and can be microbially synthesized from renewable carbon streams. Its production has been demonstrated in Pseudomonas putida KT2440 but its titers, rates, and yields have yet to reach commercially viable levels, potentially due to toxicity to the bacterial chassis. We hypothesized that utilization of Tolerization Adaptive Laboratory Evolution (TALE) would generate P. putida hosts more tolerant to isoprenol and suitable for enhanced production phenotypes. Here, we performed a comprehensive TALE campaign using three strains, the wild-type and two strains lacking subsets of known isoprenol catabolism and transport functions in quadruplicate independently evolved lineages. Several evolved clones from each starting strain displayed robust growth (up to 0.2 h<sup>-1</sup>) at 8 g/L of isoprenol, where starting strains could not grow. Whole genome resequencing of the 12 independent strain lineages identified convergent mutations. Reverse engineering each of the four commonly mutated regions individually (gnuR, ttgB-PP_1394, PP_3024-PP_5558, PP_1695) resulted in a partial recovery of the tolerance phenotypes observed in the evolved strains. Additionally, a proteomics-guided deletion of the master motility regulator, fleQ, in an evolved clone alleviated the tolerance vs. production trade-off, restoring isoprenol titers and consumption to levels observed in the starting strains. Collectively, this work demonstrated that an integrated strategy of laboratory evolution and rational engineering was effective to develop robust biofuel production hosts with minimized product toxicity.</p>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120112","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}

引用次数: 0

Efficient biosynthesis of gallic acid by a syntrophic Escherichia coli co-culture system 大肠杆菌共培养系统高效合成没食子酸的研究。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-16 DOI: 10.1016/j.ymben.2025.05.005

Shucai Wang , Zexi Kong , Xuecheng Xu , Jian Zhang , Liangcai Lin , Fengli Wu , Qinhong Wang

{"title":"Efficient biosynthesis of gallic acid by a syntrophic Escherichia coli co-culture system","authors":"Shucai Wang , Zexi Kong , Xuecheng Xu , Jian Zhang , Liangcai Lin , Fengli Wu , Qinhong Wang","doi":"10.1016/j.ymben.2025.05.005","DOIUrl":"10.1016/j.ymben.2025.05.005","url":null,"abstract":"<div><div>Gallic acid (GA), a natural phenolic acid antioxidant, has significant therapeutic and industrial applications. However, its traditional manufacturing approach, based on plant extraction, has been associated with risks of environmental pollution as well as a limited range of applications. Consequently, microbial-based production of GA, being more environmental-friendly, is viewed as a potential alternative. This study reports the efficient biosynthesis of GA from renewable glucose via a syntrophic <em>Escherichia coli</em> co-culture system. An effective GA biosynthesis pathway was first analyzed and determined. Then the rate-limiting step involving the hydroxylation of protocatechuic acid (PCA) to GA was removed by integrating multiple copies of the key gene <em>pobA</em><sup>T294A/Y385F</sup> into the chromosome of a PCA-overproducing strain. The resulting strain GA10 produced 41.88 g/L GA with a yield of 0.185 mol/mol, but up to 9.54 g/L of the intermediate PCA accumulated in the fermentation broth. To overcome this issue, a catalytic strain COT03 was constructed by coupling the metabolism of excess intracellular NADPH supply with the NADPH-consuming reaction catalyzed by PobA<sup>T294A/Y385F</sup>. This yielded a syntrophic <em>E</em>. <em>coli</em> co-culture system that consisted of a GA-overproducing strain (GA10) and a growth-coupled biocatalytic strain (COT03). Following optimization of the culture conditions, the co-culture system produced 57.66 g/L GA from glucose within 75 h, with a yield of 0.233 mol/mol and an average productivity of 0.769 g/L/h. This study lays the foundation for the potential industrial biomanufacturing of GA from glucose.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 313-321"},"PeriodicalIF":6.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087525","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}

引用次数: 0

Engineering Yarrowia lipolytica for enhanced lipid productivity in nutrient-rich conditions: A scalable approach to microbial lipid production 在营养丰富的条件下提高脂质产量的工程解脂耶氏菌：一种可扩展的微生物脂质生产方法。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-13 DOI: 10.1016/j.ymben.2025.05.004

Dongpil Lee , Hyemin Park , Jae-Eung Kim , Yeonsoo Kim , Joo Hyun Park , Hyesoo Lee , Byoung Hoon Yoon , Boyoung Han , Joon Young Jung , Seungwoo Cha , Peter Lee , Ji-Sook Hahn

{"title":"Engineering Yarrowia lipolytica for enhanced lipid productivity in nutrient-rich conditions: A scalable approach to microbial lipid production","authors":"Dongpil Lee , Hyemin Park , Jae-Eung Kim , Yeonsoo Kim , Joo Hyun Park , Hyesoo Lee , Byoung Hoon Yoon , Boyoung Han , Joon Young Jung , Seungwoo Cha , Peter Lee , Ji-Sook Hahn","doi":"10.1016/j.ymben.2025.05.004","DOIUrl":"10.1016/j.ymben.2025.05.004","url":null,"abstract":"<div><div>Climate change is reducing crop yields and increasing price volatility for commodities like cocoa and palm oil, thereby driving the need for sustainable alternatives such as microbial lipid production. The oleaginous yeast <em>Yarrowia lipolytica</em> is a promising platform for lipid synthesis. However, its lipid accumulation has traditionally relied on nitrogen limitation, posing challenges for achieving high yields under nutrient-rich conditions. In this study, we engineered <em>Y. lipolytica</em> to enhance lipid accumulation and productivity in nutrient-rich environments. Key modifications included deleting <em>MHY1</em> to prevent filamentous growth, overexpressing triacylglycerol (TAG) biosynthetic genes, disrupting fatty acid degradation, and redirecting phosphatidic acid flux toward TAG biosynthesis by reducing phospholipid production through <em>OPI3</em> deletion and <em>CDS1</em> mutation. Furthermore, deletion of <em>CEX1</em> to block citrate excretion significantly enhanced lipid accumulation. The resulting strain, CJ0415, achieved a lipid production of 54.6 g/L with a lipid content of 45.8 % and a record lipid productivity of 2.06 g/L/h under nutrient-rich conditions in a 5-L fermenter, representing a 2.6-fold increase compared to nitrogen-limited conditions. These findings underscore the potential of <em>Y. lipolytica</em> as a robust platform for scalable, industrial lipid production under nutrient-rich conditions.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 302-312"},"PeriodicalIF":6.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065812","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}

引用次数: 0

Enhancing the production of isopropanol with reduced CO2 emission via protein and metabolic engineering using Corynebacterium glutamicum 利用谷氨酸棒状杆菌的蛋白质和代谢工程提高异丙醇的生产和减少二氧化碳排放。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-13 DOI: 10.1016/j.ymben.2025.05.006

Wu-Young Jeong , Eunseo In , Myeong-Eun Lee , Young Jin Ko , Sung Ok Han

{"title":"Enhancing the production of isopropanol with reduced CO2 emission via protein and metabolic engineering using Corynebacterium glutamicum","authors":"Wu-Young Jeong , Eunseo In , Myeong-Eun Lee , Young Jin Ko , Sung Ok Han","doi":"10.1016/j.ymben.2025.05.006","DOIUrl":"10.1016/j.ymben.2025.05.006","url":null,"abstract":"<div><div>Isopropanol (IPA), a versatile chemical with applications in various fields of industries, yet its petroleum-based production raises environmental concerns. In this study, <em>Corynebacterium glutamicum</em> was engineered to enhance IPA production while mitigating CO<sub>2</sub> emissions. First, the rational design of secondary alcohol dehydrogenase (SADH) variants with shifted cofactor specificity from NADPH to NADH, resulting in an 11.11-fold increased NADH oxidation rate and 6.02-fold increased enzyme activity. Secondly, modified SADH was used in combination with the <em>Ncgl1676</em> promoter in order to separate the growth and production phases. This engineering resulted in a strain called CGIPA-4, which showed a 2.45-fold increase in IPA production. To address CO<sub>2</sub> emission, carbonic anhydrase from <em>Hydrogenovibrio marinus</em> (<em>HmCA</em>) and acetoacetyl-CoA synthase (<em>nphT7</em>) were overexpressed, constructing CGIPA-5 strain, enabling conversion of CO<sub>2</sub> into bicarbonate, which supported IPA biosynthesis and reduced emissions by up to 21 %. Finally, high cell density fed-batch fermentation using CGIPA-5 strain produced 148.6 ± 3.8 g L<sup>−1</sup> IPA, with CO<sub>2</sub> emission reduced by 30 % compared to CGIPA-4 strain. This work demonstrates a sustainable approach to petrochemical replacement through protein and metabolic engineering.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 267-275"},"PeriodicalIF":6.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065814","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}

引用次数: 0

Metabolic engineering of acetogenic bacteria using CO gas-sensing transcriptional ON/OFF modules 利用CO气敏转录ON/OFF模块的产丙酮菌代谢工程。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-10 DOI: 10.1016/j.ymben.2025.04.012

Sangrak Jin , Irisappan Ganesh , Jiyun Bae , Donghwi Lee , Seulgi Kang , Hyeonsik Lee , Jeong Wook Lee , Byung-Kwan Cho

{"title":"Metabolic engineering of acetogenic bacteria using CO gas-sensing transcriptional ON/OFF modules","authors":"Sangrak Jin , Irisappan Ganesh , Jiyun Bae , Donghwi Lee , Seulgi Kang , Hyeonsik Lee , Jeong Wook Lee , Byung-Kwan Cho","doi":"10.1016/j.ymben.2025.04.012","DOIUrl":"10.1016/j.ymben.2025.04.012","url":null,"abstract":"<div><div>Dynamic sensing of gas substrates like toxic carbon monoxide (CO) in living microbial cells is often limited due to the lack of suitable biosensors. Here, we integrated the CO-binding transcription activators, CooA and RcoM1, with an O<sub>2</sub>-independent fluorescent reporter system, Halo-tag, to develop CO-sensing modules (ON/OFF) capable of detecting CO concentrations in the strictly anaerobic acetogenic bacterium <em>Eubacterium limosum</em>. Furthermore, we employed CooA as the CO-sensing ON module to activate the target genes for 2,3-butanediol (2,3-BDO) biosynthesis, achieving a 1.7-fold increase in 2,3-BDO yield. These results indicate that the CO-ON module effectively redirects carbon flux toward target product biosynthesis pathway in acetogens. However, during CO gas with glucose mixotrophic fermentation, lactate emerged as the predominant product. To enhance target pathway flux using the CO-ON module, we deleted the lactate pathway in <em>E. limosum</em> using CRISPR/Cas9. The resulting engineered strain showed an 18.5 % increase in carbon utilization for 2,3-BDO production under CO sensing culture conditions. This optimized platform strain subsequently produced approximately 52 g/L of 2,3-BDO during two stage CO-glucose mixotrophic fermentation. Our results provide orthogonal CO-sensing transcriptional regulatory modules for engineering metabolic pathways that efficiently convert CO into value-added biochemicals using acetogenic biocatalysts.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 290-301"},"PeriodicalIF":6.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945092","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}

引用次数: 0

Proteome trade-off between primary and secondary metabolism shapes acid stress induced bacterial exopolysaccharide production 初级和次级代谢之间的蛋白质组权衡形成酸胁迫诱导的细菌胞外多糖生产

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-10 DOI: 10.1016/j.ymben.2025.05.002

Sizhe Qiu , Aidong Yang , Xinyu Yang , Haojie Ni , Wenlu Li , Zhennai Yang , Hong Zeng , Yanbo Wang

{"title":"Proteome trade-off between primary and secondary metabolism shapes acid stress induced bacterial exopolysaccharide production","authors":"Sizhe Qiu , Aidong Yang , Xinyu Yang , Haojie Ni , Wenlu Li , Zhennai Yang , Hong Zeng , Yanbo Wang","doi":"10.1016/j.ymben.2025.05.002","DOIUrl":"10.1016/j.ymben.2025.05.002","url":null,"abstract":"<div><div>Bacterial exopolysaccharide (EPS), as a high-value probiotic product, is known to be biosynthesized by a secondary metabolic pathway to mediate acid stress in lactic acid bacteria. However, a quantitative understanding of cellular resource coordination underlying acid stress-induced EPS production remains lacking. Systematically investigating <em>Lactiplantibacillus plantarum</em> HMX2, a well acknowledged EPS-producer, this study measured growth phenotypes, metabolomics, and proteomics of the target strain cultured at different pH values. Multi-omics analysis demonstrated that the EPS biosynthetic pathway was significantly up-regulated under acid stress, and pinpointed Fur as the most probable controlling transcriptional factor. Furthermore, the experimentally observed proteome re-allocation between primary metabolism and EPS biosynthesis was effectively captured by the regulatory proteome constrained flux balance analysis (RPCFBA) model via incorporating an activation function for secondary metabolism. This work, fusing the power of multi-omics analysis and genome-scale metabolic modeling, quantitatively elucidated the proteome trade-off between cellular growth and stress resistance underlying EPS production in lactic acid bacteria and shed light on the control principle of microbial secondary metabolism.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 254-266"},"PeriodicalIF":6.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948124","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}

引用次数: 0

Engineering oleaginous yeast Rhodotorula toruloides for production of alkanes and alkenes 用于生产烷烃和烯烃的工程产油酵母。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-07 DOI: 10.1016/j.ymben.2025.05.003

Yi Yu , Quan Yuan , Jing Dai , Huimin Zhao , Shuobo Shi

{"title":"Engineering oleaginous yeast Rhodotorula toruloides for production of alkanes and alkenes","authors":"Yi Yu , Quan Yuan , Jing Dai , Huimin Zhao , Shuobo Shi","doi":"10.1016/j.ymben.2025.05.003","DOIUrl":"10.1016/j.ymben.2025.05.003","url":null,"abstract":"<div><div>Due to limited reserves and excessive carbon emission of fossil fuels, there has been an increasing interest in developing advanced biofuels with high energy density such as alkanes and alkenes. Here we report the design and construction of three heterologous biosynthetic pathways of alkanes and alkenes in oleaginous yeast <em>Rhodotorula toruloides</em>, including the AAR/ADO, UndA/UndB and FAP pathways. The performance of various enzymes from different organisms was evaluated within <em>R. toruloides</em> for each pathway. Various metabolic engineering strategies were used to enhance the production of alkanes and alkenes across all three pathways, including enzyme screening, byproduct elimination, and precursor supply enhancement. Notably, the FAP pathway demonstrated significantly superior performance compared to the AAR/ADO and UndA/UndB pathway. As a result, 1.73 g/L alkanes and alkenes were produced from glucose, and 0.94 g/L alkanes and alkenes were produced from lignocellulosic hydrolysates, representing the highest alkanes and alkenes titers reported in yeast. This work establishes <em>R. toruloides</em> as a promising host for hydrocarbons production from glucose and CO<sub>2</sub>-neutral feedstocks and paves the way for further strain and process optimization towards industrial production of alkanes and alkenes.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 242-253"},"PeriodicalIF":6.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932519","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}

引用次数: 0

Beyond CEN.PK - parallel engineering of selected S. cerevisiae strains reveals that superior chassis strains require different engineering approaches for limonene production 超出岑。对选定的酿酒酵母菌株进行PK -平行工程研究表明，优良的底盘菌株需要不同的工程方法来生产柠檬烯。

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-05 DOI: 10.1016/j.ymben.2025.04.011

Yanmei Zhu , Sasha Yogiswara , Anke Willekens , Agathe Gérardin , Rob Lavigne , Alain Goossens , Vitor B. Pinheiro , Zongjie Dai , Kevin J. Verstrepen

{"title":"Beyond CEN.PK - parallel engineering of selected S. cerevisiae strains reveals that superior chassis strains require different engineering approaches for limonene production","authors":"Yanmei Zhu , Sasha Yogiswara , Anke Willekens , Agathe Gérardin , Rob Lavigne , Alain Goossens , Vitor B. Pinheiro , Zongjie Dai , Kevin J. Verstrepen","doi":"10.1016/j.ymben.2025.04.011","DOIUrl":"10.1016/j.ymben.2025.04.011","url":null,"abstract":"<div><div>Genetically engineered microbes are increasingly utilized to produce a broad range of high-value compounds. However, most studies start with only a very narrow group of genetically tractable type strains that have not been selected for maximum titers or industrial robustness. In this study, we used high-throughput screening and parallel metabolic engineering to identify and optimize <em>Saccharomyces cerevisiae</em> chassis strains for the production of limonene, a monoterpene with applications in flavors, fragrances, and biofuels. We screened 921 genetically and phenotypically distinct <em>S. cerevisiae</em> strains for limonene tolerance and lipid content to identify optimal chassis strains for precision fermentation of limonene. In parallel, we also evaluated 16 different plant limonene synthases. Our results revealed that two of the selected strains showed approximately a 2-fold increase in titers compared to CEN.PK2-1C, the type strain that is often used as a chassis for limonene production, with the same genetic modifications in the mevalonate pathway. Intriguingly, the most effective engineering strategy proved strain-specific. Metabolic profiling revealed that this difference is likely explained by differences in native mevalonate production. Ultimately, by using strain-specific engineering strategies, we achieved 844 mg/L in a new strain, 40 % higher than the titer (605 mg/L) achieved by CEN.PK2-1C. Our findings demonstrate the potential of leveraging genetic diversity in <em>S. cerevisiae</em> for monoterpene bioproduction and highlight the necessity for tailoring metabolic engineering strategies to specific strains.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 276-289"},"PeriodicalIF":6.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920985","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}

引用次数: 0

Corrigendum to “Insights into the methanol utilization capacity of Y. lipolytica and improvements through metabolic engineering” [Metabol. Eng. (2025) 91 30–43] “解脂Y.酵母的甲醇利用能力及其通过代谢工程的改进”的勘误表[代谢。Eng。（2025） 91 - 43]

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-02 DOI: 10.1016/j.ymben.2025.04.004

Wei Jiang , William Newell , Jingjing Liu , Lucas Coppens , Khushboo Borah Slater , Huadong Peng , David Bell , Long Liu , Victoria Haritos , Rodrigo Ledesma-Amaro

引用次数: 0

Photosynthetic sorbitol production in Synechococcus sp. PCC 7002 is enhanced by addressing phosphatase promiscuity, nutrient availability and Calvin cycle bottlenecks 聚球菌PCC 7002通过解决磷酸酶混杂性、养分有效性和卡尔文循环瓶颈，提高了光合作用山梨醇的产量

IF 6.8 1区生物学

Metabolic engineering Pub Date : 2025-05-02 DOI: 10.1016/j.ymben.2025.04.008

Cody Kamoku , Pranav Bhavaraju , Collin Travis , Luis Taquillo , David R. Nielsen

{"title":"Photosynthetic sorbitol production in Synechococcus sp. PCC 7002 is enhanced by addressing phosphatase promiscuity, nutrient availability and Calvin cycle bottlenecks","authors":"Cody Kamoku , Pranav Bhavaraju , Collin Travis , Luis Taquillo , David R. Nielsen","doi":"10.1016/j.ymben.2025.04.008","DOIUrl":"10.1016/j.ymben.2025.04.008","url":null,"abstract":"<div><div>Cyanobacteria represent promising biocatalysts for producing carbohydrates, including sorbitol, a naturally-occurring, fermentable sugar alcohol with conventional uses as a sweetener, pharmaceutical additive, and biodegradable plasticizer. Previously, <em>Synechocystis</em> sp. PCC 6803 was engineered to produce sorbitol, reaching a final titer of 2.3 g/L after 18 days. To improve upon this performance, sorbitol production was herein engineered in the faster growing strain <em>Synechococcus</em> sp. PCC 7002. Upon introducing the sorbitol biosynthetic pathway, up to 500 mg/L sorbitol was initially produced after seven days. However, due to the initial use of two highly promiscuous sugar phosphatase variants, this also resulted in the unwanted co-production of ribose and growth inhibition due to depletion of ribose-5-phosphate from the Calvin cycle. This off-target effect was ultimately mitigated via the discovery that mannitol-1-phosphate phosphatase from <em>Eimeria tenella</em> also dephosphorylates sorbitol-6-phosphate to sorbitol with greater specificity, leading to improved growth and sorbitol production. Next, two bottleneck enzymes in the Calvin cycle, namely fructose-bisphosphate aldolase (FBA) and bifunctional fructose-1,6-bisphosphatase/sedoheptulose-1,7-bisphosphatase (BiBPase), were overexpressed both individually and in combination, resulting in sorbitol production up to 1.3 g/L. Finally, upon optimizing the culture media to address nutrient limitation, the final strain produced up to 3.6 g/L sorbitol in nine days, respectively representing 1.5- and 3-fold increases in titer and productivity relative to previously-engineered <em>Synechocystis</em> sp. PCC 6803.</div></div>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":"91 ","pages":"Pages 181-191"},"PeriodicalIF":6.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911542","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}

引用次数: 0