Synthetic and Systems Biotechnology最新文献_第2页

CRISPR/Cas12a-based genome editing for cyanophage of Anabeana sp. 基于 CRISPR/Cas12a 的蓝藻噬菌体基因组编辑技术

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-10-03 DOI: 10.1016/j.synbio.2024.09.011

Shengjian Yuan , Yanchen Li , Chunhua Kou , YiChen Sun , Yingfei Ma

{"title":"CRISPR/Cas12a-based genome editing for cyanophage of Anabeana sp.","authors":"Shengjian Yuan , Yanchen Li , Chunhua Kou , YiChen Sun , Yingfei Ma","doi":"10.1016/j.synbio.2024.09.011","DOIUrl":"10.1016/j.synbio.2024.09.011","url":null,"abstract":"<div><div>Efforts have been conducted on cyanobacterial genome editing, yet achieving genome editing in cyanophages remains challenging. Editing cyanophage genomes is crucial for understanding and manipulating their interactions with cyanobacterial hosts, offering potential solutions for controlling cyanobacterial blooms. In this study, we developed a streamlined CRISPR-Cas12a-based method for efficient cyanophage genome editing and then applied this method to the cyanophages A-1(L) and A-4(L) of <em>Anabeana</em> sp. PCC.7120. Multiple hypothetical genes were edited and knocked out from these two cyanophage genomes, generating viable mutants with varying capabilities to inhibit cyanobacterial growth. All these mutants displayed significant inhibitory effects on the host, indicating that these genes were non-essential for phage life cycle and the deletion led to little impairment of the cyanophages in infectious efficiency to their host. By iterative and simultaneous gene knockouts in cyanophage A-4(L), we achieved the minimal genome mutant with a 2400 bp reduction in genome size, representing a 5.75 % decrease compared to the wild type (WT). In conclusion, these cyanophage mutants can facilitate the identification of nonessential genes for cyanophages biology and the insertion of foreign genes for synthetic biology research. This advancement holds promise in addressing the widespread issue of water blooms and the associated environmental hazards.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 140-147"},"PeriodicalIF":4.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developing polycistronic expression tool in Yarrowia lipolytica 在脂溶性亚罗酵母中开发多聚组蛋白表达工具

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-28 DOI: 10.1016/j.synbio.2024.09.010

Donghan Li , Jianhui Liu , Lingxuan Sun , Jin Zhang , Jin Hou

引用次数: 0

Synthetic biotechnology for C1 bio-refinery 用于 C1 生物精炼厂的合成生物技术

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-23 DOI: 10.1016/j.synbio.2024.09.009

Yongjin Zhou (Chair Professor), Benjamin Woolston (Assistant Professor)

引用次数: 0

Transcriptome analysis reveals methanol metabolism variations for the growth damage caused by overexpression of chimeric transactivators in Pichia pastoris 转录组分析揭示了甲醇代谢变化对过量表达嵌合转录因子的 Pichia pastoris 生长造成的损害

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-23 DOI: 10.1016/j.synbio.2024.09.008

Qi Liu , Ziyu He , Menghao Cai

{"title":"Transcriptome analysis reveals methanol metabolism variations for the growth damage caused by overexpression of chimeric transactivators in Pichia pastoris","authors":"Qi Liu , Ziyu He , Menghao Cai","doi":"10.1016/j.synbio.2024.09.008","DOIUrl":"10.1016/j.synbio.2024.09.008","url":null,"abstract":"<div><div>Methanol is a promising substrate for sustainable biomanufacturing, and <em>Pichia pastoris</em> has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter. Previous reconstruction of gene circuits highly improved transcriptional activity, but excessive expression of chimeric transactivator damaged cell growth on methanol. Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regulatory networks. The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism, especially the <em>alcohol oxidase 1</em> (<em>AOX1</em>), but without remarkable changes in expression of transcriptional factors. Meanwhile, the synthesis of peroxisomes also varied with chimeric transactivator expression. In addition, the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism. The gene expression patterns caused by different expression levels of chimeric transactivators have also been clarified. This work provides useful information to understand the transcriptional regulation of the <em>AOX1</em> promoter and methanol signaling. It revealed the importance of balancing transcription factor expression for the host improvement.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 133-139"},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi 艾蒿中的β-石竹烯合成酶在酿酒酵母中高效生物合成β-石竹烯

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-22 DOI: 10.1016/j.synbio.2024.09.005

Zhengping Li , Yuhong Gan , Changyu Gou , Qiongyu Ye , Yang Wu , Yuhong Wu , Tingxing Yang , Baolian Fan , Aijia Ji , Qi Shen , Lixin Duan

{"title":"Efficient biosynthesis of β-caryophyllene in Saccharomyces cerevisiae by β-caryophyllene synthase from Artemisia argyi","authors":"Zhengping Li , Yuhong Gan , Changyu Gou , Qiongyu Ye , Yang Wu , Yuhong Wu , Tingxing Yang , Baolian Fan , Aijia Ji , Qi Shen , Lixin Duan","doi":"10.1016/j.synbio.2024.09.005","DOIUrl":"10.1016/j.synbio.2024.09.005","url":null,"abstract":"<div><div><em>Artemisia argyi</em> H. Lév. & Vaniot is an important traditional Chinese medicinal plant known for its volatile oils, which are the main active components of <em>A. argyi</em>, including monoterpenes, sesquiterpenes and their derivatives. Despite its medicinal significance, the biosynthesis of sesquiterpenoids in <em>A. argyi</em> remains underexplored. In this study, we identified four <em>β</em>-caryophyllene synthases from <em>A. argyi.</em> A high-yield <em>β</em>-caryophyllene engineered <em>Saccharomyces cerevisiae</em> cell factory has been built in this study. By fusing <em>ERG20</em> and <em>AarTPS88</em> with a flexible linker (GGGS)<sub>2</sub> and enhancing metabolic flux in the MVA pathway (<em>HIF-1</em>, <em>tHMGR</em>, and <em>UPC2-1</em>), we achieved a titer of <em>β</em>-caryophyllene reached 15.6 g/L by fed-batch fermentation in a 5 L bioreactor. To our knowledge, this represents the highest reported titer of <em>β</em>-caryophyllene in yeast to date. This study provides a valuable tool for the industrial-scale production of <em>β</em>-caryophyllene.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 158-164"},"PeriodicalIF":4.4,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a green Komagataella phaffii cell factory for sustainable production of plant-derived sesquiterpene (–)-α-bisabolol 开发绿色 Komagataella phaffii 细胞工厂，以可持续方式生产植物源倍半萜 (-)-α-bisabolol

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-17 DOI: 10.1016/j.synbio.2024.09.006

Jintao Cheng , Zhongji Pu , Jiali Chen , Dingfeng Chen , Baoxian Li , Zhengshun Wen , Yuanxiang Jin , Yanlai Yao , Kan Shao , Xiaosong Gu , Guiling Yang

{"title":"Development of a green Komagataella phaffii cell factory for sustainable production of plant-derived sesquiterpene (–)-α-bisabolol","authors":"Jintao Cheng , Zhongji Pu , Jiali Chen , Dingfeng Chen , Baoxian Li , Zhengshun Wen , Yuanxiang Jin , Yanlai Yao , Kan Shao , Xiaosong Gu , Guiling Yang","doi":"10.1016/j.synbio.2024.09.006","DOIUrl":"10.1016/j.synbio.2024.09.006","url":null,"abstract":"<div><div>(–)-α-Bisabolol is a plant-derived sesquiterpene derived from <em>Eremanthus erythropappus,</em> which can be used as a raw material in cosmetics and has anti-inflammatory function. In this study, we designed six mutation sites of the (–)-α-bisabolol synthase BOS using the plmDCA algorithm. Among these, the F324Y mutation demonstrated exceptional performance, increasing the product yield by 73 %. We constructed a <em>de novo</em> (–)-α-bisabolol biosynthesis pathways through systematic synthetic biology strategies, including the enzyme design of BOS, selection of different linkers in fusion expression, and optimization of the mevalonate pathway, weakening the branching metabolic flow and multi-copy strategies, the yield of (–)-α-bisabolol was significantly increased, which was nearly 35-fold higher than that of the original strain (2.03 mg/L). The engineered strain was capable of producing 69.7 mg/L in shake flasks. To the best of our knowledge, this is the first report on the biosynthesis of (–)-α-bisabolol in <em>Komagataella phaffii</em>, implying this is a robust cell factory for sustainable production of other terpenoids.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 120-126"},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional investigation of the SAM-dependent methyltransferase RdmB in anthracycline biosynthesis 蒽环类生物合成中依赖于 SAM 的甲基转移酶 RdmB 的功能研究

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-12 DOI: 10.1016/j.synbio.2024.09.002

Moli Sang , Qingyu Yang , Jiawei Guo , Peiyuan Feng , Wencheng Ma , Wei Zhang

{"title":"Functional investigation of the SAM-dependent methyltransferase RdmB in anthracycline biosynthesis","authors":"Moli Sang , Qingyu Yang , Jiawei Guo , Peiyuan Feng , Wencheng Ma , Wei Zhang","doi":"10.1016/j.synbio.2024.09.002","DOIUrl":"10.1016/j.synbio.2024.09.002","url":null,"abstract":"<div><p>A novel sub-class of <em>S</em>-adenosyl-<span>l</span>-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from <em>Streptomyces purpurascens,</em> it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4-<em>O</em>-methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4-<em>O</em>-methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.</p></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 102-109"},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405805X24001212/pdfft?md5=2b156fbb5e3c9f4fbd7f97ed291fe436&pid=1-s2.0-S2405805X24001212-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Predicting effective drug combinations for cancer treatment using a graph-based approach 利用基于图的方法预测治疗癌症的有效药物组合

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-11 DOI: 10.1016/j.synbio.2024.09.003

Qi Wang , Xiya Liu , Guiying Yan

{"title":"Predicting effective drug combinations for cancer treatment using a graph-based approach","authors":"Qi Wang , Xiya Liu , Guiying Yan","doi":"10.1016/j.synbio.2024.09.003","DOIUrl":"10.1016/j.synbio.2024.09.003","url":null,"abstract":"<div><div>Drug combination therapy, involving the use of two or more drugs, has been widely employed to treat complex diseases such as cancer. It enhances therapeutic efficacy, reduces drug resistance, and minimizes side effects. However, traditional methods to identify effective drug combinations are time-consuming, costly, and less efficient than computational methods. Therefore, developing computational approaches to predict drug combinations has become increasingly important.</div><div>In this paper, we developed the Random Walk with Restart for Drug Combination (RWRDC) model to predict effective drug combinations for cancer therapy. The RWRDC model offers a quantitative mathematical method for predicting the potential effective drug combinations. Cross-validation results indicate that the RWRDC model outperforms other predictive models, particularly in breast, colorectal, and lung cancer predictions across various performance metrics. We have theoretically proven the convergence of its algorithm and provided an explanation for the algorithm's rationality. A targeted case study on breast cancer further highlights the capability of RWRDC to identify effective drug combinations. These findings highlight our model as a novel and effective tool for discovering potential effective drug combinations, offering new possibilities in therapy. Additionally, the graph-based framework of RWRDC holds potential for predicting drug combinations in other complex diseases, expanding its utility in the medical field.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 148-155"},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the physiological properties of baker's yeast based on single-cell Raman spectrum technology 基于单细胞拉曼光谱技术评估面包酵母的生理特性

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-11 DOI: 10.1016/j.synbio.2024.09.004

Xi Sun , Xin Zhou , Ran Yu , Xiaofang Zhou , Jun Zhang , Teng Xu , Jianmei Wang , Mengqi Li , Xiaoting Li , Min Zhang , Jian Xu , Jia Zhang

{"title":"Assessing the physiological properties of baker's yeast based on single-cell Raman spectrum technology","authors":"Xi Sun , Xin Zhou , Ran Yu , Xiaofang Zhou , Jun Zhang , Teng Xu , Jianmei Wang , Mengqi Li , Xiaoting Li , Min Zhang , Jian Xu , Jia Zhang","doi":"10.1016/j.synbio.2024.09.004","DOIUrl":"10.1016/j.synbio.2024.09.004","url":null,"abstract":"<div><div>With rapid progress in the yeast fermentation industry, a comprehensive commercial yeast quality assessment approach integrating efficiency, accuracy, sensitivity, and cost-effectiveness is required. In this study, a new yeast quality assessment method based on single-cell Raman technology was developed and contrasted with traditional methods. The findings demonstrated significant associations (Pearson correlation coefficient of 0.933 on average) between the two methods in measuring physiological indicators, including cell viability and intracellular trehalose content, demonstrating the credibility of the Raman method compared to the traditional method. Furthermore, the sensitivity of the Raman method in viable but non-culturable cells was higher in measuring yeast cell viability (17.9 % more sensitive). According to the accurate quantitative analysis of metabolic activity level (MAL) of yeast cells, the cell vitality was accurately quantified at population and single-cell levels, offering a more comprehensive assessment of yeast fermentation performance. Overall, the single-cell Raman method integrates credibility, feasibility, accuracy, and sensitivity in yeast quality assessment, offering a new technological framework for quality assessments of live-cell yeast products.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 110-118"},"PeriodicalIF":4.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered probiotic-mediated intratumoral delivery and controlled release of bacterial collagenase for cancer therapy 工程益生菌介导的肿瘤内输送和细菌胶原酶控释用于癌症治疗

IF 4.4 2区生物学

Synthetic and Systems Biotechnology Pub Date : 2024-09-06 DOI: 10.1016/j.synbio.2024.09.001

Hong-Rui Li, Bang-Ce Ye

{"title":"Engineered probiotic-mediated intratumoral delivery and controlled release of bacterial collagenase for cancer therapy","authors":"Hong-Rui Li, Bang-Ce Ye","doi":"10.1016/j.synbio.2024.09.001","DOIUrl":"10.1016/j.synbio.2024.09.001","url":null,"abstract":"<div><div>Elevated collagen levels within breast tumors are strongly associated with tumor progression and present a barrier to effective therapeutic agent penetration within the tumor microenvironment (TME), leading to poor clinical outcomes. To address this challenge, we engineered a probiotic strain to degrade collagen within the TME by selectively colonizing in tumors and releasing bacterial collagenase in a lysis-dependent manner. Initially, we constructed a therapeutic bacterial strain designed to lyse within the TME and release an encoded immunotoxin comprising a nanobody targeting CD47 (CD47nb) and a modified <em>Pseudomonas</em> exotoxin A (PE38KDEL). The introduction of collagenase-expressing bacteria, in conjunction with therapeutic immunotoxin, reduced collagen fiber levels within the TME, resulting in inhibited tumor growth and prolonged survival in a murine model of breast cancer. Furthermore, we investigated the broader applicability of the collagenase-expressing bacterial strain in combination with chemotherapeutic drugs, such as doxorubicin. Remarkably, synergistic antitumor effects were observed in mice treated with this combination therapy. In conclusion, our study demonstrates that probiotic delivery of bacterial collagenase offers a promising adjuvant treatment strategy for selectively degrading intratumoral collagen, thereby improving the efficacy of anticancer therapies in breast cancer.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages 226-236"},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142659617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0