Synthetic and Systems Biotechnology最新文献

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MicroDFBEST: A dCas12b-derived dual-function base editor with programmable editing characteristics for microbial genetic engineering MicroDFBEST:一种dcas12b衍生的双功能碱基编辑器,具有可编程编辑特性,用于微生物基因工程
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2026-03-01 Epub Date: 2025-09-12 DOI: 10.1016/j.synbio.2025.09.013
Wen-Liang Hao , De-Zhi Geng , Yu-Feng Liu , Lai-Chuang Han , Zhe-Min Zhou , Wen-Jing Cui
{"title":"MicroDFBEST: A dCas12b-derived dual-function base editor with programmable editing characteristics for microbial genetic engineering","authors":"Wen-Liang Hao ,&nbsp;De-Zhi Geng ,&nbsp;Yu-Feng Liu ,&nbsp;Lai-Chuang Han ,&nbsp;Zhe-Min Zhou ,&nbsp;Wen-Jing Cui","doi":"10.1016/j.synbio.2025.09.013","DOIUrl":"10.1016/j.synbio.2025.09.013","url":null,"abstract":"<div><div>Base editors (BEs) enable precise genome editing, but their use in microbes remains limited by restricted mutagenesis capabilities and narrow editing windows. Here, we reported MicroDFBEST, a novel dual-function base editor (DFBE) for microbes, by fusing the high-activity deaminases evoCDA1 and TadA9 with nuclease-deficient Cas12b from <em>Bacillus hisashii</em> (dBhCas12b). This engineered system enables simultaneous C-to-T and A-to-G editing within a 26–33 nt window, the broadest range reported for microbial DFBEs. The editing characteristics of MicroDFBEST can be easily adjusted by changing fusion protein expression and editing generations to create diverse mutant libraries. We show that the MicroDFBEST system enables both flexible gene expression modulation via random promoter (P<sub><em>ylbP</em></sub>) diversification and targeted protein evolution through mutational hotspot scanning in native genomic contexts. This study offers a versatile platform enabling in situ gene regulation (e.g., biosynthetic gene clusters activation) and protein evolution (e.g., chassis optimization), with broad synthetic biology utility.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"11 ","pages":"Pages 161-171"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096565","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}
引用次数: 0
A near-infrared ratio fluorescent probe achieves mitochondrial hydrogen polysulfide imaging for monitoring ferroptosis in arthritis 近红外比例荧光探针实现线粒体多硫化氢成像监测关节炎中的铁下垂
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2026-03-01 Epub Date: 2025-09-02 DOI: 10.1016/j.synbio.2025.08.016
Ting Cao , Ziwen Xiao , Wenhua Dong , Hong Ma , Deyan Gong , Zhefeng Fan
{"title":"A near-infrared ratio fluorescent probe achieves mitochondrial hydrogen polysulfide imaging for monitoring ferroptosis in arthritis","authors":"Ting Cao ,&nbsp;Ziwen Xiao ,&nbsp;Wenhua Dong ,&nbsp;Hong Ma ,&nbsp;Deyan Gong ,&nbsp;Zhefeng Fan","doi":"10.1016/j.synbio.2025.08.016","DOIUrl":"10.1016/j.synbio.2025.08.016","url":null,"abstract":"<div><div>Reactive sulfur (RSS) is a type of sulfur-containing molecule widely present in biological systems. Hydrogen polysulfide (H<sub>2</sub>S<sub>n</sub>, n &gt; 1), as a member of the active sulfur family, plays an indispensable role in many physiological and pathological processes. Ferroptosis is a special cell death mode driven by iron-dependent lipid peroxidation, which is involved in the occurrence and development of various human diseases. Ferroptosis is manifested by increased lipid peroxidation and elevated levels of reactive oxygen species (ROS), which further lead to an increase in H<sub>2</sub>S<sub>n</sub> content in cells. Emerging research suggests a close association between ferroptosis and arthritis related diseases. This work successfully constructed a mitochondrial-targeted ratiometric near-infrared fluorescent probe for the specific detection of H<sub>2</sub>S<sub>n</sub>. The experimental results show that the probe (<strong>Cy-S<sub>4</sub></strong>) has a large Stokes shift (∼218 nm), excellent optical properties, extremely fast response time (8 s), high sensitivity (DL = 0.23 μM), and strong specificity. This probe has been successfully applied to tracking the content of H<sub>2</sub>S<sub>n</sub> in ferroptosis process and fluorescence imaging of H<sub>2</sub>S<sub>n</sub> in inflammatory cell mitochondria. Pathological section data confirmed that the probe has good <em>in vivo</em> imaging ability, and more importantly, <em>in vivo</em> arthritis imaging experiments showed that the expression of H<sub>2</sub>S<sub>n</sub> plays an important role in ferroptosis. These experimental results will provide a reliable monitoring tool for the treatment and prevention of arthritis, enriching the theoretical research related to this disease.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"11 ","pages":"Pages 59-67"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046581","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}
引用次数: 0
Developing the protein quality control system in Streptomyces for selective translation of ultra-long full-length polyketide synthase mRNAs to enhance biosynthesis efficiency 建立链霉菌超长全长聚酮合成酶mrna选择性翻译的蛋白质量控制系统,提高生物合成效率
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2026-03-01 Epub Date: 2025-10-15 DOI: 10.1016/j.synbio.2025.10.004
Chanjuan Jiang , Kexin Hao , Shaoqian Wang , Ruofei Guo , Xiaochen Li , Lin Lv , Ji Luan , Hailong Wang
{"title":"Developing the protein quality control system in Streptomyces for selective translation of ultra-long full-length polyketide synthase mRNAs to enhance biosynthesis efficiency","authors":"Chanjuan Jiang ,&nbsp;Kexin Hao ,&nbsp;Shaoqian Wang ,&nbsp;Ruofei Guo ,&nbsp;Xiaochen Li ,&nbsp;Lin Lv ,&nbsp;Ji Luan ,&nbsp;Hailong Wang","doi":"10.1016/j.synbio.2025.10.004","DOIUrl":"10.1016/j.synbio.2025.10.004","url":null,"abstract":"<div><div>Genes that encode type I polyketide synthases (PKSs), which synthesize an array of invaluable drugs, typically exceed 10 kilobases in length. Truncated messenger RNAs (mRNAs) have been demonstrated to constitute the majority of PKS mRNAs; However, a method for the selective translation of full-length PKS mRNAs has yet to be established. Here we developed a protein quality control system in <em>Streptomyces</em> to selectively translate ultra-long full-length PKS mRNAs for enhanced biosynthesis efficiency. The <em>Streptomyces</em> protein quality control (strProQC) system comprises the switch RNA, which encapsulates the start codon and the ribosome binding site within a secondary structure, and the trigger RNA, which is the complementary counterpart to the switch RNA. The trigger RNA is placed at the 3′ end of the mRNA so that it can hybridize with the switch RNA to expose the translation-initiation region to ribosomes, enabling translation initiation. Truncated mRNAs do not contain the <em>cis</em>-trigger at their 3′ ends, therefore, their translation cannot be initiated and full-length mRNAs are selectively translated. We initially identified strong terminators and switch-trigger pairs to establish the strProQC system. Then the switch sequences in the strProQC system were further optimized by exchanging ribosome binding sites to improve the ON state strength by 2.8 folds and the ON/OFF ratio by 31.6 folds. Finally, the refined strProQC system was utilized for the selective translation of the full-length mRNAs of the 7.8-kb spinosad PKS gene (<em>spnA</em>) and the 25.7-kb rapamycin PKS gene (<em>rapA</em>). This resulted in a 1.4-fold increase in spinosad yields and a 4.7-fold increase in rapamycin yields, respectively, when compared to the yields obtained from the nonselective translation of both full-length and truncated PKS mRNAs.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"11 ","pages":"Pages 323-332"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416667","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}
引用次数: 0
From consultors to collaborators – An SOP for advancing ethics engagement in science 从顾问到合作者——促进科学伦理参与的标准操作程序
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-06-23 DOI: 10.1016/j.synbio.2025.06.006
Varsha Aravind Paleri, Kristien Hens
{"title":"From consultors to collaborators – An SOP for advancing ethics engagement in science","authors":"Varsha Aravind Paleri,&nbsp;Kristien Hens","doi":"10.1016/j.synbio.2025.06.006","DOIUrl":"10.1016/j.synbio.2025.06.006","url":null,"abstract":"<div><div>Synthetic Biology (SynBio) is an interdisciplinary field that tackles global challenges in healthcare, sustainability, food production, among others. However, it also presents critical ethical concerns, including biosecurity, justice, and the unintended consequences of research biases. Addressing these concerns requires timely and systematic ethical evaluation. Conventional approaches often relegate ethics to an external, procedural role rather than embedding it within the core of scientific inquiry, leading to delayed engagement and associated challenges. This article introduces a structured, stage-wise Standard Operating Procedure (SOP) to support the systematic integration of ethics into scientific research. Particularly beneficial for early-career researchers and ethicists, this framework offers a practical method for incorporating ethical reflection throughout the research process.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1180-1189"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535762","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}
引用次数: 0
Engineered bacteriophage-based bioimaging Technology: Development and applications 基于工程噬菌体的生物成像技术:发展与应用
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-08-06 DOI: 10.1016/j.synbio.2025.07.009
Yuanzhao Shen , Lichang Sun , Jun Li , Xin Zhou , Ran Wang
{"title":"Engineered bacteriophage-based bioimaging Technology: Development and applications","authors":"Yuanzhao Shen ,&nbsp;Lichang Sun ,&nbsp;Jun Li ,&nbsp;Xin Zhou ,&nbsp;Ran Wang","doi":"10.1016/j.synbio.2025.07.009","DOIUrl":"10.1016/j.synbio.2025.07.009","url":null,"abstract":"<div><div>Engineered bacteriophages (phages) have emerged as powerful and versatile tools for bioimaging, owing to their natural specificity for bacterial targets and their amenability to functional modification. This review summarizes recent advances in the development and application of phage-based imaging probes, with a particular focus on surface functionalization techniques and genetic engineering strategies used to construct functional phage imaging agents. These engineered phage probes have been applied across diverse imaging modalities, including fluorescence, magnetic resonance imaging (MRI), nuclear imaging, near-infrared (NIR) optical imaging, and surface-enhanced Raman scattering (SERS), etc. and have been utilized to enable highly sensitive detection of bacterial pathogens, improved diagnosis of infectious diseases, and monitoring of tissue engineering processes. Despite these innovations, critical challenges remain in ensuring robust target specificity, precise control of labeling stoichiometry, and favorable biocompatibility. Addressing issues such as non-specific probe binding, signal quenching, and immunogenicity will be crucial to fully realize the potential of phage-based bioimaging. Looking ahead, this review discusses future directions for next-generation phage imaging platforms with enhanced specificity, multiplexed functionality, and improved translational potential for clinical diagnostics.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1352-1367"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865773","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}
引用次数: 0
Transcriptomic studies on the product stress response revealed that YCF1 is a beneficial factor for progesterone production in Yarrowia lipolytica 对产物胁迫反应的转录组学研究表明,YCF1是脂耶氏菌产生孕酮的有益因子
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-04-17 DOI: 10.1016/j.synbio.2025.04.008
Ying Wang , Ruosi Zhang , Mingdong Yao , Wenhai Xiao , Ying Wang , Ying-Jin Yuan
{"title":"Transcriptomic studies on the product stress response revealed that YCF1 is a beneficial factor for progesterone production in Yarrowia lipolytica","authors":"Ying Wang ,&nbsp;Ruosi Zhang ,&nbsp;Mingdong Yao ,&nbsp;Wenhai Xiao ,&nbsp;Ying Wang ,&nbsp;Ying-Jin Yuan","doi":"10.1016/j.synbio.2025.04.008","DOIUrl":"10.1016/j.synbio.2025.04.008","url":null,"abstract":"<div><div>Progesterone is a widely used therapeutic hormone and a common precursor for the synthesis of pharmaceutical steroids in both mammals and plants. It has been successfully produced in heterologous microorganisms, but the market demand has not been met. The low progesterone yield, possibly due to product stress, may put pressure on the growth of strains and limit product synthesis efficiency. In this study, key pathways and genes that cause changes in amino acid and lipid metabolism and protein transport were identified through omics analysis. The expression of transporters leads to increased progesterone production and alleviated growth inhibition. Two related genes (gene IDs: 2912325 and 2908366) encoding the transporters glpF and SNQ2 improved production by 29.2 % and 51.7 %, respectively. Isoenzymes of native and exogenous transporters were screened and overexpressed. YCF1 from <em>Saccharomyces cerevisiae</em> exhibited the greatest benefit, increasing progesterone synthesis by 69.6 %. Our findings help reveal the impact of product stress on cellular metabolism and processes, providing research directions and literature support for the synthesis of other products.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1087-1097"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271522","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}
引用次数: 0
Engineering a drug-inducible pyroptosis platform enables precise tumor suppression in colorectal cancer 设计一个药物诱导的焦亡平台可以精确抑制结直肠癌的肿瘤
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-08-14 DOI: 10.1016/j.synbio.2025.08.004
Xiang Yao , Yu Wei , Yuan Gao , Lei Li , Junchi Liu , Wenmin Zhou , Tao Yan , Letian Gong , Yang Zhou , Ganglong Gao
{"title":"Engineering a drug-inducible pyroptosis platform enables precise tumor suppression in colorectal cancer","authors":"Xiang Yao ,&nbsp;Yu Wei ,&nbsp;Yuan Gao ,&nbsp;Lei Li ,&nbsp;Junchi Liu ,&nbsp;Wenmin Zhou ,&nbsp;Tao Yan ,&nbsp;Letian Gong ,&nbsp;Yang Zhou ,&nbsp;Ganglong Gao","doi":"10.1016/j.synbio.2025.08.004","DOIUrl":"10.1016/j.synbio.2025.08.004","url":null,"abstract":"<div><div>Colorectal cancer remains a leading cause of cancer-related mortality, with long-term survival rates hindered by chemoresistance and an immunosuppressive tumor microenvironment. Gene-based therapies offer high specificity but are limited by challenges such as off-target effects, inefficient delivery, and systemic toxicity. Here, we report the design and functional validation of a chemically inducible gene circuit that harnesses Gasdermin E (GSDME) to trigger pyroptotic cell death on demand. We substituted its native proteolytic activation motif with a customized protease recognition sequence. By engineering inducible protease variants whose activity is tightly regulated by an orally bioavailable, clinically approved small molecule, we achieved precise temporal control of pyroptosis. In patient-derived organoid models, administration of the inducer led to rapid GSDME cleavage, pore formation, and robust cell lysis. In a xenograft model, oral treatment with the approved drug led to marked tumor growth inhibition. This strategy utilizes the safety and pharmacokinetics of an approved drug to enable programmable cell death, providing a versatile platform for the targeted elimination of treatment-resistant tumors.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1388-1397"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891998","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}
引用次数: 0
Engineering non-P450 3-hydroxylase for de novo synthesizes catechol-containing compounds in Escherichia coli 工程非p450 3-羟化酶在大肠杆菌中重新合成含儿茶酚的化合物
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-08-05 DOI: 10.1016/j.synbio.2025.07.014
Xing-Run Zheng, Guan-Peng Li, Qian-Hui Chen, Jian-Zhong Liu
{"title":"Engineering non-P450 3-hydroxylase for de novo synthesizes catechol-containing compounds in Escherichia coli","authors":"Xing-Run Zheng,&nbsp;Guan-Peng Li,&nbsp;Qian-Hui Chen,&nbsp;Jian-Zhong Liu","doi":"10.1016/j.synbio.2025.07.014","DOIUrl":"10.1016/j.synbio.2025.07.014","url":null,"abstract":"<div><div>Catechols (such as <span>l</span>-DOPA, caffeic acid and hydroxytyrosol, etc.) are a class of phenolic derivatives with ortho-hydroxyl groups which represents various bioactivities including antioxidative, anti-inflammatory, antiviral, and anticancer properties. Non-P450-dependent 3′-hydroxylases HpaBC are the rate-limiting enzymes in catechol biosynthesis. Herein, different HpaB/HpaC combinations were first investigated. The best combinations of KpHpaB from <em>Klebsiella pneumoniae</em> and PaHpaC from <em>Pseudomonas aeruginosa</em> (or SeHpaC from <em>Salmonella enterica</em>) were obtained for the <em>de novo</em> synthesis of <span>l</span>-DOPA in <em>E. coli</em>, resulting in 1838.56 mg/L <span>l</span>-DOPA (or 1822.99 mg/L <span>l</span>-DOPA). The highest production of caffeic acid and hydroxytyrosol were obtained with the enzyme combinations of PaHpaB from <em>P. aeruginosa</em> and SeHpaC from <em>S</em>. <em>enterica,</em> and PlHpaB from <em>Photorhabdus luminescens</em> and KpHpaC from <em>K. pneumoniae</em>, respectively. Next, PaHpaB and PlHpaB were further engineered to improve their catalytic efficiency by the semi-rational method. PaHpaB<sup>A211W</sup> and PlHpaB<sup>S210G</sup> were obtained. The titer of caffeic acid was further increased to 1281.25 mg/L without <span>l</span>-DOPA accumulation using the PaHpaB<sup>A211W</sup>-UTR-SeHpaC hybrid. The production of hydroxytyrosol was further enhanced to 1681.42 mg/L using the combination of PlHpaB<sup>S210G</sup>-UTR- KpHpaC. The production of <span>l</span>-DOPA, caffeic acid and hydroxytyrosol was increased using these hybrids of HpaB/HpaC by 4.6-fold, 10.1-fold, and 8.4-fold compared to EcHpaBC from <em>Escherichia coli</em>, respectively. This work demonstrates that pairing of HpaB/HpaC and engineering HpaB is an powerful method for improving 3-hydroxylase activity and the production of catechol-containing compounds.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1294-1305"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841792","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}
引用次数: 0
Recombinant production of amaranthin and other betalain variants with yeast cell factories 用酵母细胞工厂重组生产苋菜素和其他甜菜素变体
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-05-21 DOI: 10.1016/j.synbio.2025.05.008
Christiane Glitz, Jane Dannow Dyekjær, Gian Maria Cristian Solimando, Paulo Marcelo Avila Neto, Daniela Rago, Mahsa Babaei, Irina Borodina
{"title":"Recombinant production of amaranthin and other betalain variants with yeast cell factories","authors":"Christiane Glitz,&nbsp;Jane Dannow Dyekjær,&nbsp;Gian Maria Cristian Solimando,&nbsp;Paulo Marcelo Avila Neto,&nbsp;Daniela Rago,&nbsp;Mahsa Babaei,&nbsp;Irina Borodina","doi":"10.1016/j.synbio.2025.05.008","DOIUrl":"10.1016/j.synbio.2025.05.008","url":null,"abstract":"<div><div>Betalains are a class of natural pigments found in plants of the Caryophyllales order. Betanin is the dominant betalain on the food colour market, even though over 80 other variants are known. Recombinant production of betanin has recently gained interest as a cost-efficient and sustainable alternative to traditional plant extraction, but the production of other betalain variants remains largely unexplored. We selected three glucuronosyltransferases from <em>Amaranthus hypochondriacus</em>, <em>Chenopodium quinoa</em> and <em>Celosia argentea</em> var. <em>cristata</em> and screened the enzymes <em>in vivo</em> in betanin-producing <em>Saccharomyces cerevisiae</em>. Instead of producing amaranthin, two of the enzymes led to the formation of the betalain bougainvillein-rI (betanidin 5-O-β-sophoroside). When expressed together with a UDP-dehydrogenase that allowed the synthesis of UDP-glucuronic acid, each enzyme converted betanin to amaranthin. Integration of the glucuronosyltransferases in a <em>Yarrowia lipolytica</em> betanin producer strain directly resulted in amaranthin production. In fed-batch fermentation, 2.97 g/L ± 29.3 mg/L of amaranthin was produced. Co-expression of the glucuronosyltransferases with a malonyltransferase from <em>Hylocereus polyrhizus</em> led to the formation of 6′-O-malonyl-amaranthin in <em>S. cerevisiae</em> and <em>Y. lipolytica</em>. This study expands the portfolio of natural food colourants that can efficiently be produced through microbial fermentation and contributes to elucidating the biosynthesis pathway of betalains.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1127-1139"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321107","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}
引用次数: 0
Metabolic engineering of Escherichia coli for squalene overproduction 过量生产角鲨烯的大肠杆菌代谢工程
IF 4.4 2区 生物学
Synthetic and Systems Biotechnology Pub Date : 2025-12-01 Epub Date: 2025-06-07 DOI: 10.1016/j.synbio.2025.06.003
Jiangming Zhu , Yaping Mao , Hongchun Mo , Xuehui Dai , Yuhan Wu , Guangyi Wang , Zhanguang Feng , Ruirui Yue , Dongzhi Wei , Haili Liu , Yong Wang
{"title":"Metabolic engineering of Escherichia coli for squalene overproduction","authors":"Jiangming Zhu ,&nbsp;Yaping Mao ,&nbsp;Hongchun Mo ,&nbsp;Xuehui Dai ,&nbsp;Yuhan Wu ,&nbsp;Guangyi Wang ,&nbsp;Zhanguang Feng ,&nbsp;Ruirui Yue ,&nbsp;Dongzhi Wei ,&nbsp;Haili Liu ,&nbsp;Yong Wang","doi":"10.1016/j.synbio.2025.06.003","DOIUrl":"10.1016/j.synbio.2025.06.003","url":null,"abstract":"<div><div>Squalene, a lipophilic triterpene with multifaceted bioactivities, faces bioproduction bottlenecks in microbial hosts due to inefficient biosynthetic pathways and limited storage capacity. Here, we address these challenges through systems metabolic engineering integrating redox-balanced 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) variants and membrane lipid remodeling. By developing a hybrid HMGRs system combining NADPH-dependent and NADH-preferred enzymes, squalene production reached 852.06 ± 28.95 mg/L with balanced cofactor utilization. Subsequent engineering of membrane morphology and lipid metabolism generated lipid-enriched elongated cells, through the overexpression of <em>dgs</em>, <em>murG</em> and <em>plsC</em>, boosting squalene production to 970.86 ± 55.67 mg/L. Implementation of delayed induction strategies coupled with 10 % dodecane overlay as an <em>in situ</em> recovery system achieved a final squalene titer of 1267.01 mg/L in a 3 L bioreactor. Mechanistic studies revealed fatty acid (FA) and phosphatidylethanolamine (PE) as key reservoirs for squalene in <em>E</em>. <em>coli</em>, with <em>dgs</em> overexpression specifically promoting cellular elongation. This article provides comprehensive insights into engineering strategies and mechanistic perspectives, establishing a universal framework for hydrophobic metabolite biomanufacturing in prokaryotic hosts.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 4","pages":"Pages 1119-1126"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314259","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}
引用次数: 0
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