{"title":"Thank you Reviewers","authors":"","doi":"10.1016/S2405-805X(25)00030-4","DOIUrl":"10.1016/S2405-805X(25)00030-4","url":null,"abstract":"","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 1","pages":"Pages I-III"},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855221","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}
Jinyan Huo , Xiaohui Chu , Bo Hong , Ruo Lv , Xiaoyu Wang , Jianxu Li , Ge Jiang , Baomin Feng , Zongxia Yu
{"title":"Exploration and mutagenesis of the germacrene A synthase from Solidago canadensis to enhance germacrene A production in E. coli","authors":"Jinyan Huo , Xiaohui Chu , Bo Hong , Ruo Lv , Xiaoyu Wang , Jianxu Li , Ge Jiang , Baomin Feng , Zongxia Yu","doi":"10.1016/j.synbio.2025.02.015","DOIUrl":"10.1016/j.synbio.2025.02.015","url":null,"abstract":"<div><div>β-elemene is an effective anti-cancer component which has been widely used in clinic. However, it still relies on the extraction from the Chinese medicine plant <em>Curcuma wenyujin</em>, which seriously limits its application. Synthetic biology offers a promising approach to satisfy its supply. β-elemene is derived from germacrene A (GA), which is synthesized by germacrene A synthase (GAS), through Cope rearrangement under heat condition instead of enzymatic reaction. In this study, an effective germacrene A synthase (ScGAS) was identified from <em>Solidago canadensis</em> which could produce GA when expressed in <em>E.</em> <em>coli</em>. By introducing the heterogeneous MVA pathway to enrich the FPP pool, the strain yielded 147 mg/L of GA in shake flasks which represented 2.98-fold improvement over the initial one. Moreover, combining molecular docking with phylogeny analysis of ScGAS largely narrowed down the category of its key residues' mutagenesis. The Y376L mutant showed the highest yield of 487 mg/L which was almost 10-fold higher than the initial yield. These results indicate that diverting the metabolism of the host and enzyme mutagenesis based on the combination of molecular docking and phylogeny analysis are of great value to constructing terpenoids chassis.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 620-628"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594257","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}
{"title":"The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla","authors":"Yaran Suo , Shuyu Li , Haining Lyu , Xin Zhao, Jiale Xing, Xin Chai, Qian Zhang, Chunjin Fu, Chengchao Xu, Jingjing Liao","doi":"10.1016/j.synbio.2025.02.013","DOIUrl":"10.1016/j.synbio.2025.02.013","url":null,"abstract":"<div><div>Natural products from medicinal plants serve as an invaluable resource for drug discovery and development. However, low-abundance natural products are often understudied due to the challenges of obtaining sufficient quantities for pharmacological testing in cells or animals. Additionally, their complex stereochemistry and functional groups make chemical synthesis and purification difficult. In this study, we showcased the power of biosynthetic approaches to explore these underexplored compounds, using the low-abundance polyphyllin trillin 6′-<em>O</em>-glucoside from <em>Paris polyphylla</em> as an example. We identified two trillin 6′-<em>O</em>-glucosyltransferases required for its biosynthesis and successfully reconstructed the entire pathway in <em>Nicotiana benthamiana</em>. We demonstrated that trillin 6′-<em>O</em>-glucoside exhibits anti-bacterial activity comparable to major polyphyllins like polyphyllins I, II, and VII. Notably, it also showed much lower hemolytic activity, a common side effect of those major polyphyllins. Together, our study underscores the advantages of employing biosynthetic approaches to explore natural products that exist in low or trace abundances yet possess equally important pharmacological activities.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 610-619"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594256","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}
Chalak Najat Abdullah , Mengsu Liu , Qihang Chen , Song Gao , Changtai Zhang , Shike Liu , Jingwen Zhou
{"title":"Efficient production of astaxanthin in Yarrowia lipolytica through metabolic and enzyme engineering","authors":"Chalak Najat Abdullah , Mengsu Liu , Qihang Chen , Song Gao , Changtai Zhang , Shike Liu , Jingwen Zhou","doi":"10.1016/j.synbio.2025.02.014","DOIUrl":"10.1016/j.synbio.2025.02.014","url":null,"abstract":"<div><div>Astaxanthin is a natural red carotenoid, commonly used as an additive in the pharmaceutical industry and as a nutritional supplement owing to its notable antioxidant benefits. However, a complex biosynthetic pathway poses a challenge to <em>de novo</em> biosynthesis of astaxanthin. Here, <em>Yarrowia lipolytica</em> was engineered through multiple strategies for high level production of astaxanthin using a cheap mineral medium. For the production of β-carotene, a platform strain was constructed in which 411.7 mg/L of β-carotene was produced at a shake-flask level. Integration of algal β-carotene ketolase and β-carotene hydroxylase led to the production of 12.3 mg/L of astaxanthin. Furthermore, construction of <em>HpBKT</em> and <em>HpCrtZ</em> as a single enzyme complex along with the enhanced catalytic activity of the enzymes led to the accumulation of 41.0 mg/L of astaxanthin. Iterative gene integration into the genome and direction of the astaxanthin production pathway into sub-organelles substantially increased astaxanthin production (172.1 mg/L). Finally, restoration of the auxotrophic markers and medium optimization further improved astaxanthin production to 237.3 mg/L. The aforementioned approaches were employed in fed-batch fermentation to produce 2820 mg/L of astaxanthin (229-fold improvement regarding the starter strain), with an average productivity of 434 mg/L/d and a yield of 5.6 mg/g glucose, which is the highest reported productivity in <em>Y. lipolytica</em>.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 737-750"},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776813","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}
Jinbo Xiang , Mengsu Liu , Xinglong Wang , Mingyu Yue , Zhijie Qin , Jingwen Zhou
{"title":"Combined metabolic and enzymatic engineering for de novo biosynthesis of δ-tocotrienol in Yarrowia lipolytica","authors":"Jinbo Xiang , Mengsu Liu , Xinglong Wang , Mingyu Yue , Zhijie Qin , Jingwen Zhou","doi":"10.1016/j.synbio.2025.02.011","DOIUrl":"10.1016/j.synbio.2025.02.011","url":null,"abstract":"<div><div>δ-Tocotrienol, an isomer of vitamin E with anti-inflammatory, neuroprotective and anti-coronary arteriosclerosis properties, is widely used in health care, medicine and other fields. Microbial synthesis of δ-tocotrienol offers significant advantages over plant extraction and chemical synthesis methods, including increased efficiency, cost-effectiveness and environmental sustainability. However, limited precursor availability and low catalytic efficiency of key enzymes remain major bottlenecks in the biosynthesis of δ-tocotrienol. In this study, we assembled the complete δ-tocotrienol biosynthetic pathway in <em>Yarrowia lipolytica</em> and enhanced the precursor supply, resulting in a titre of 102.8 mg/L. The catalytic efficiency of the rate-limiting steps in the pathway was then enhanced through various strategies, including fusion expression of key enzymes homogentisate phytyltransferaseand and tocopherol cyclase, semi-rational design of SyHPT and multi-copy integration of pathway genes. The final a δ-tocotrienol titre in a 5 L bioreactor was 466.8 mg/L following fed-batchfermentation. This study represents the first successful <em>de novo</em> biosynthesis of δ-tocotrienol in <em>Y. lipolytica</em>, providing valuable insights into the synthesis of vitamin E-related compounds.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 3","pages":"Pages 719-727"},"PeriodicalIF":4.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776811","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}
Zirong Zhu , Li Cao , Ziyuan Xia , Xirong Liu , Wangqion Chen , Zirui Dai , Duo Jin , Jie Rang , Shengbiao Hu , Liqiu Xia
{"title":"CRISPRi-mediated multigene downregulating redirects the metabolic flux to spinosad biosynthesis in Saccharopolyspora spinosa","authors":"Zirong Zhu , Li Cao , Ziyuan Xia , Xirong Liu , Wangqion Chen , Zirui Dai , Duo Jin , Jie Rang , Shengbiao Hu , Liqiu Xia","doi":"10.1016/j.synbio.2025.02.010","DOIUrl":"10.1016/j.synbio.2025.02.010","url":null,"abstract":"<div><div>Microorganisms are often likened to complex production workshops. In <em>Saccharopolyspora spinosa</em> (<em>S. spinosa</em>), the biosynthesis of spinosad is a production line within its intricate workshop. Optimizing the entire production environment and reducing unnecessary metabolic flow is essential to increasing spinosad yield. Pyruvate serves as a crucial precursor for spinosad biosynthesis. Previous studies revealed that the <em>pyc</em> gene is highly expressed in the gluconeogenic pathway, leading to a pyruvate shunt. By downregulating <em>pyc</em>, we enhanced spinosad yield, although the improvement was below expectations. We speculated that most of the accumulated pyruvate following the <em>pyc</em> knockdown entered some synthetic pathways unrelated to spinosad. Through metabolic pathway and qRT-PCR analyses, we found that the expression levels of <em>gltA1</em> and <em>atoB3</em> within the pyruvate metabolic tributary, including the TCA cycle and ethylmalonyl-CoA pathway, were significantly increased in the <em>pyc</em> knockdown strain. The combined knockdown of these three genes optimized the spinosad production line, increasing its yield to 633.1 ± 38.6 mg/L, representing a 199.4 % increase. This study identifies three key genes for optimizing spinosad biosynthesis and offers insights into gene screening and the efficient construction of Spinosad-producing strains.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 583-592"},"PeriodicalIF":4.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510367","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}
Wei Jiang , Yijian Guo , Xuanshuo Liang , Ying Zhang , Jianning Kang , Zhengxin Jin , Bin Ning
{"title":"A dual light-controlled co-culture system enables the regulation of population composition","authors":"Wei Jiang , Yijian Guo , Xuanshuo Liang , Ying Zhang , Jianning Kang , Zhengxin Jin , Bin Ning","doi":"10.1016/j.synbio.2025.02.012","DOIUrl":"10.1016/j.synbio.2025.02.012","url":null,"abstract":"<div><div>With the development of metabolic engineering, increasing requirements for efficient microbial biosynthesis call for establishment of multi-strain co-culture system. Dynamic regulation of population ratios is crucial for optimizing bioproduction performance. Optogenetic systems with high universality and flexibility have the potential to realize dynamic control of population proportion. In this study, we utilized an optimized chromatic acclimation sensor/regulator (CcaS/R) system and a blue light-activated YF1-FixJ-PhlF system as induction modules. A pair of orthogonal quorum sensing systems and a toxin-antitoxin system were employed as communication module and effector module, respectively. By integrating these modules, we developed a dual light-controlled co-culture system that enables dynamic regulation of population ratios. This co-culture system provides a universal toolkit for applications in metabolic engineering and synthetic biology.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 574-582"},"PeriodicalIF":4.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510221","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}
{"title":"Modulating ion channels with nanobodies","authors":"Sher Ali , Ashley Suris , Yun Huang , Yubin Zhou","doi":"10.1016/j.synbio.2025.02.005","DOIUrl":"10.1016/j.synbio.2025.02.005","url":null,"abstract":"<div><div>Ion channels play instrumental roles in regulating membrane potential and cross-membrane signal transduction, thus making them attractive targets for understanding various physiological processes and associated diseases. Gaining a deeper understanding of their structural and functional properties has significant implications for developing therapeutic interventions. In recent years, nanobodies, single-domain antibody fragments derived from camelids, have emerged as powerful tools in ion channel and synthetic biology research. Their small size, high specificity, and ability to recognize difficult-to-reach epitopes offer advantages over conventional antibodies and biologics. Furthermore, their resemblance to the variable region of human IgG family III reduces immunogenicity concerns. Nanobodies have introduced new opportunities for exploring ion channel structure-function relationships and offer a promising alternative to conventional drugs, which often face challenges such as off-target effects and toxicity. This review highlights recent progress in applying nanobodies to interrogate and modulate ion channel activity, with an emphasis on their potential to overcome current technical and therapeutic limitations.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 593-599"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510222","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}
Tingfeng Cheng , Xinyan Cao , Yuchen Wang , Lei Zhao
{"title":"Development of CRISPR-Cas9-based genome editing tools for non-model microorganism Erwinia persicina","authors":"Tingfeng Cheng , Xinyan Cao , Yuchen Wang , Lei Zhao","doi":"10.1016/j.synbio.2025.02.006","DOIUrl":"10.1016/j.synbio.2025.02.006","url":null,"abstract":"<div><div><em>Erwinia persicina</em> is a bacterium that has been known to produce secondary metabolites, such as andrimid, pink pigment, and exopolysaccharides, and to infect more than twenty plant species. However, traditional gene manipulation methods have been hindered by the inefficient of suicide plasmid-mediated genome editing. In this study, we describe the successful application of the CRISPR-Cas9 system in <em>E. persicina</em>. Efficient genome editing was achieved by substituting the native gRNA promoter with J23119 in a single-plasmid system (pRed_Cas9_Δ<em>poxB</em>) and optimizing the gRNA design. The use of double gRNAs led to the deletion of a 42 kb genomic fragment, and the incorporation of a <em>sacB</em> screening marker facilitated iterative knockouts. Additionally, a 22 kb plasmid containing a self-resistance gene was conjugally transferred into <em>E. persicina</em>, resulting in the insertion of a 6.4 kb fragment with 100 % efficiency. Furthermore, we demonstrated the expression of shinorine, an anti-UV compound, within the <em>E. persicina</em> chassis. This study establishes <em>E. persicina</em> as a promising chassis for synthetic biology and provides a model for gene-editing systems in non-model microorganisms.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 555-563"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487995","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}
Jinhong Zhao , Fangyuan Guo , Mengqi Wang , Jie Zhang , Sanjun Ying , Ying Gao , Gensheng Yang , Weiyong Hong
{"title":"The advancement of biosensor design and construction utilizing biomolecular motors","authors":"Jinhong Zhao , Fangyuan Guo , Mengqi Wang , Jie Zhang , Sanjun Ying , Ying Gao , Gensheng Yang , Weiyong Hong","doi":"10.1016/j.synbio.2025.02.007","DOIUrl":"10.1016/j.synbio.2025.02.007","url":null,"abstract":"<div><div>Biomolecular motors have been extensively studied as efficient molecular machines in detection systems owing to their unique signal conversion mechanisms and high energy conversion efficiencies. The application of these motors in the detection of pathogenic microorganisms is particularly promising. Through reasonable design and optimization, biomolecular motors can enable precise and efficient detection, enhancing clinical diagnostics. This paper reviews recent advances in detection systems utilizing various biomolecular motors, including kinesin, dynein, myosin, DNA polymerase, F<sub>o</sub>F<sub>1</sub>-ATPase, and flagellar motors. Detection mechanisms involving these motors are also introduced. Furthermore, the review covers recent progress in detecting antigens, antibodies, bacteria, and small molecules using biomolecular motors. Finally, the challenges and future prospects of biomolecular motor-based detection systems for pathogenic microorganisms are discussed, highlighting their potential as rapid and efficient tools for applications in food safety and medicine.</div></div>","PeriodicalId":22148,"journal":{"name":"Synthetic and Systems Biotechnology","volume":"10 2","pages":"Pages 543-554"},"PeriodicalIF":4.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480002","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}