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Remodeling Isoprene Pyrophosphate Metabolism for Promoting Terpenoids Bioproduction

Engineering 2023年第9期28卷 166-178页

作者： Xianhao Xu Xueqin Lv Shixiu Cui Yanfeng Liu Hongzhi Xia Jianghua Li Guocheng Du Zhaofeng Li Rodrigo Ledesma-Amaro Jian Chen Long Liu Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationJiangnan UniversityWuxi 214122China Science Center for Future Foods Ministry of EducationJiangnan UniversityWuxi 214122China Richen Bioengineering Co. Ltd.Nantong 226000China State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China Department of Bioengineering and Centre for Synthetic Biology Imperial College LondonLondon SW72AZUK

Terpenoids are the largest family of natural *** are made from the building block isoprene pyrophosphate(IPP),and their bioproduction using engineered cell factories has received a great deal of *** date,the insufficient metabolic supply of IPP remains a great challenge for the efficient synthesis of *** this work,we discover that the imbalanced metabolic flux distribution between the central metabolism and the IPP supply hinders IPP accumulation in Bacillus subtilis(***).Therefore,we remodel the IPP metabolism using a series of genetically encoded two-input-multioutput(TIMO)circuits that are responsive to pyruvate or/and malonyl-CoA,resulting in an IPP pool that is significantly increased by up to *** a proof-of-concept validation,we design an IPP metabolism remodeling strategy to improve the production of three valuable terpenoids,including menaquinone-7(MK-7,4.1-fold),lycopene(9-fold),andβ-carotene(0.9-fold).In particular,the titer of MK-7 in a 50-L bioreactor reached 1549.6 mg·L^(-1),representing the highest titer reported so ***,we propose a TIMO genetic circuits-assisted IPP metabolism remodeling framework that can be generally used for the synergistic fine-tuning of complicated metabolic modules to achieve the efficient bioproduction of terpenoids.

关键词： Terpenoids genetic circuits Bacillus subtilis Isoprene pyrophosphate

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An integrative database and its application for plant synthetic biology research

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Plant Communications 2024年第5期5卷 123-133页

作者： Chenfei Tian Jianhua Li Yuhan Wu Guangyi Wang Yixin Zhang Xiaowei Zhang Yuwei Sun Yong Wang CAS-Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China University of Chinese Academy of Sciences Beijing 100039China College of Life Science Jilin Agricultural UniversityChangchun 130118China

Plant synthetic biology research requires diverse bioparts that facilitate the redesign and construction of new-to-nature biological devices or systems in *** by few well-characterized bioparts for plant chassis,the development of plant synthetic biology lags behind that of its microbial ***,we constructed a web-based Plant Synthetic BioDatabase(PSBD),which currently categorizes 1677 catalytic bioparts and 384 regulatory elements and provides information on 309 species and 850 *** bioinformatics tools including local BLAST,chem similarity,phylogenetic analysis,and visual strength are provided to assist with the rational design of genetic circuits for manipulation of gene expression in *** demonstrated the utility of the PSBD by functionally characterizing taxadiene synthase 2 and its quan-titative regulation in tobacco *** powerful synthetic devices were then assembled to amplify the transcriptional signals,enabling enhanced expression ofﬂavivirus non-structure 1 proteins in *** PSBD is expected to be an integrative and user-centered platform that provides a one-stop service for diverse applications in plant synthetic biology research.

关键词： plant synthetic biology bioparts bioinformatics tools regulation genetic circuits

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Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

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Synthetic and Systems Biotechnology 2018年第2期3卷 90-96页

作者： Lihong Jiang Jiarun Zhao Jiazhang Lian Zhinan Xu Key Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027China

Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past ***,due to complexity of cellular metabolism,the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic ***,cell-free protein synthesis system(CFPS)has been emerging as an enabling alternative to address challenges in *** review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits(biosensors)to speed up design-build-test(DBT)cycles of metabolic engineering and synthetic biology.

关键词： Cell-free protein synthesis Metabolic pathway optimization genetic circuits Metabolic engineering Synthetic biology

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From qualitative to quantitative:the state of the art and challenges for plant synthetic biology

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Quantitative Biology 2023年第3期11卷 214-230页

作者： Chenfei Tian Jianhua Li Yong Wang CAS-Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China University of Chinese Academy of Sciences Beijing 100039China

Backgrounds:As an increasing number of synthetic switches and circuits have been created for plant systems and of synthetic products produced in plant chassis,plant synthetic biology is taking a strong foothold in agriculture and *** ever-exploding data has also promoted the expansion of toolkits in this *** parts libraries and quantitative characterization approaches have been ***,plant synthetic biology is still in its *** considerations for selecting biological parts to design and construct genetic circuits with predictable functions remain ***:In this article,we review the current biotechnological progresses in field of plant synthetic *** standardization and quantitative approaches of genetic parts and genetic circuits are *** also highlight the main challenges in the iterative cycles of design-build-test-learn for introducing novel traits into ***:Plant synthetic biology promises to provide important solutions to many issues in agricultural production,human health care,and environmental ***,tremendous challenges exist in this *** example,the quantitative characterization of genetic parts is limited;the orthogonality and the transfer functions of circuits are unpredictable;and also,the mathematical modeling-assisted circuits design still needs to improve predictability and *** challenges are expected to be resolved in the near future as interests in this field are intensifying.

关键词： plant synthetic biology quantitative characterization genetic parts genetic circuits

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