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Inter-chromosomal insertions into wild-type chromosomes induced by SCRaMbLE

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Frontiers of Chemical Science and Engineering 2024年第9期18卷 125-135页

作者： Sijie Zhou Junyanrui Li Xichen Cui Ying Wang Ying-Jin Yuan Frontiers Science center for Synthetic biology and Key Laboratory of systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China Frontiers Research Institute for Synthetic biology Tianjin UniversityTianjin 300072China

Genomic rearrangements play a crucial role in shaping biological phenotypic diversity and driving species *** chromosome rearrangement and modification by LoxP-mediated evolution(SCRaMbLE)has been applied to explore large-scale genomic rearrangements,yet it has been observed that these rearrangements occur exclusively in genomic regions containing loxPsym ***,we found that SCRaMbLE of synthetic yeast harboring synthetic chromosome V and X can generate a variety of synthetic segment insertions into wild-type chromosomes,ranging from 1 to 300 ***,it was revealed that the novel insertions impacted the transcriptional level of neighboring regions and affected the production of exemplar pathway of ***,our results improve the understanding of the ability of SCRaMbLE to generate complex structural variations in nonsynthetic regions and provide a potential model to explore genomic transposable events.

关键词： genomic rearrangements synthetic yeast genome SCRaMbLE inter-chromosomal insertions synthetic biology

DIProT:A deep learning based interactive toolkit for efficient and effective Protein design

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Synthetic and systems Biotechnology 2024年第2期9卷 217-222页

作者： Jieling He Wenxu Wu Xiaowo Wang Ministry of Education Key Laboratory of Bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijingChina

The protein inverse folding problem,designing amino acid sequences that fold into desired protein structures,is a critical challenge in biological *** numerous data-driven and knowledge-driven methods,there remains a need for a user-friendly toolkit that effectively integrates these approaches for in-silico protein *** this paper,we present DIProT,an interactive protein design *** leverages a non-autoregressive deep generative model to solve the inverse folding problem,combined with a protein structure prediction *** integration allows users to incorporate prior knowledge into the design process,evaluate designs in silico,and form a virtual design loop with human *** inverse folding model demonstrates competitive performance in terms of effectiveness and efficiency on TS50 and CATH4.2 datasets,with promising sequence recovery and inference *** studies further illustrate how DIProT can facilitate user-guided protein design.

关键词： Computational Protein design Interactive design toolkit Protein inverse folding Non-autoregressive decoding

Brain-inspired chaotic spiking backpropagation

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National Science Review 2024年第6期11卷 169-179页

作者： Zijian Wang Peng Tao Luonan Chen Key Laboratory of systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences Key Laboratory of systems biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Guangdong Institute of Intelligence Science and Technology Pazhou Laboratory(Huangpu)

Spiking neural networks(SNNs) have superior energy efficiency due to their spiking signal transmission,which mimics biological nervous systems, but they are difficult to train effectively. Although surrogate gradient-based methods offer a workable solution, trained SNNs frequently fall into local minima because they are still primarily based on gradient dynamics. Inspired by the chaotic dynamics in animal brain learning, we propose a chaotic spiking backpropagation(CSBP) method that introduces a loss function to generate brain-like chaotic dynamics and further takes advantage of the ergodic and pseudo-random nature to make SNN learning effective and robust. From a computational viewpoint, we found that CSBP significantly outperforms current state-of-the-art methods on both neuromorphic data sets(***-CIFAR10 and DVS-Gesture) and large-scale static data sets(e.g. CIFAR100 and Image Net) in terms of accuracy and robustness. From a theoretical viewpoint, we show that the learning process of CSBP is initially chaotic, then subject to various bifurcations and eventually converges to gradient dynamics,consistently with the observation of animal brain activity. Our work provides a superior core tool for direct SNN training and offers new insights into understanding the learning process of a biological brain.

关键词： spiking neural networks surrogate gradient local minima backpropagation brain-inspired learning chaos

Rational surface charge engineering of haloalkane dehalogenase for boosting the enzymatic performance in organic solvent solutions

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Chinese Journal of Chemical Engineering 2024年第1期65卷 276-285页

作者： Yin Wu Yan Sun Department of Biochemical Engineering School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology(Ministry of Education)Tianjin UniversityTianjin 300350China

Biocatalysis in organic solvents(OSs)has numerous important applications,but native enzymes in OSs often exhibit limited catalytic ***,we proposed a computation-aided surface charge engineering strategy to improve the catalytic performance of haloalkane dehalogenase DhaA in OSs based on the energetic analysis of substrate binding to the DhaA *** variants with enhanced OS resistance were obtained by replacing negative charged residues on the surface with positive charged residue(Arg).Particularly,a four-substitution variant E16R/E93R/E121R/E257R exhibited the best catalytic performance(five-fold improvement in OS resistance and seven-fold half-life increase in 40%(vol)dimethylsulfoxide).As a result,the overall catalytic performance of the variant could be at least 26 times higher than the wild-type *** spectroscopy and molecular dynamics simulation studies revealed that the residue substitution mainly enhanced OS resistance from four aspects:(a)improved the overall structural stability,(b)increased the hydrophobicity of the local microenvironment around the catalytic triad,(c)enriched the hydrophobic substrate around the enzyme molecule,and(d)lowered the contact frequency between OS molecules and the catalytic *** findings validate that computationaided surface charge engineering is an effective and ingenious rational strategy for tailoring enzyme performance in OSs.

关键词： Surface charge engineering Organic solvent resistance Molecular dynamics simulation Haloalkane dehalogenase

Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli

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Synthetic and systems Biotechnology 2024年第1期9卷 144-151页

作者： Lixia Fang Ziyi Han Xueru Feng Xueyan Hao Mengxiao Liu Hao Song Yingxiu Cao Frontiers Science center for Synthetic biology and Key Laboratory of systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China Frontiers Research Institute for Synthetic biology Tianjin UniversityChina

Transcription factor engineering has unique advantages in improving the performance of microbial cell factories due to the global regulation of gene *** analyses and reverse engineering enable learning and subsequent incorporation of novel design strategies for further ***,we identify the role of the global regulator IhfA for overproduction of free fatty acids(Ffas)using CRISPRi-facilitated reverse engineering and cellular physiological *** the differentially expressed genes in the ihfAL􀀀strain,a total of 14 beneficial targets that enhance Ffas production by above 20% are identified,which involve membrane function,oxidative stress,and *** membrane-related genes,the engineered strains obtain lower cell surface hydrophobicity and increased average length of membrane lipid *** oxidative stress-related genes,the engineered strains present decreased reactive oxygen species(ROS)*** gene modulations enhance cellular robustness and save cellular resources,contributing to Ffas *** study provides novel targets and strategies for engineering microbial cell factories with improved Ffas bioproduction.

关键词： Free fatty acids CRISPRi ihfA Cell membrane ROS

Recent progress in MOFs-based nanozymes for biosensing

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Nano Research 2024年第1期17卷 39-64页

作者： Imamdin Chandio Yongjian Ai Lei Wu Qionglin Liang MOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical biology Department of ChemistryLaboratory of Flexible Electronics TechnologyCenter for Synthetic and Systems BiologyTsinghua University-Peking University Joint Centre for Life SciencesTsinghua UniversityBeijing 100084China

Nanozymes are nanomaterials with enzyme-mimicking catalytic *** to natural enzymes,nanozymes show various properties such as easy to manufacture,stable,adjustable,and *** play key roles in biosensing,biocatalysis,and disease *** an important kind of nanozymes,metal-organic framework(MOF)-based nanozymes are receiving a lot of attention due to their structural properties and *** developing MOF with enzymes-like catalytic properties has opened new perspectives in *** review summarizes the up-to-date developments in synthesizing two-dimensional and three-dimensional MOF-based nanozymes and their applications in ***,classification of nanozymes obtained by MOFs is categorized,and different properties of MOF-based nanozymes are ***,the distinctive applications of MOF-based nanozymes in identifying various analytes are thoroughly ***,the recent challenges and progressive directions in this area are highlighted.

关键词： metal-organic frameworks nanozymes metal-organic framework (MOF)-based nanozymes biosensing analytes

Opto-fluidically multiplexed assembly and micro-robotics

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Light(Science & Applications) 2024年第3期13卷 544-554页

作者： Elena Erben Weida Liao Antonio Minopoli Nicola Maghelli Eric Lauga Moritz Kreysing Max Planck Institute of Molecular Cell biology and Genetics Dresden 01307Germany center for systems biology Dresden 01307Germany Institute of Biological and Chemical systems–Biological Information Processing.Karlsruhe Institute of Technology(KIT) Eggenstein-Leopoldshafen 76344Germany Department of Applied Mathematics and Theoretical Physics University of CambridgeCambridge CB30WAUK

Techniques for high-definition micromanipulations,such as optical tweezers,hold substantial interest across a wide range of ***,their applicability remains constrained by material properties and laser *** while microfluidic manipulations have been suggested as an alternative,their inherent capabilities are limited and further hindered by practical challenges of implementation and *** we show that the iterative application of laser-induced,localized flow fields can be used for the relative positioning of multiple micro-particles,irrespectively of their material *** to the standing theoretical proposal,our method keeps particles mobile,and we show that their precision manipulation is non-linearly accelerated via the multiplexing of temperature stimuli below the heat diffusion *** resulting flow fields are topologically rich and mathematically *** represent unprecedented microfluidic control capabilities that are illustrated by the actuation of humanoid micro-robots with up to 30 degrees of freedom,whose motions are sufficiently well-defined to reliably communicate personal characteristics such as gender,happiness and *** results constitute high-definition micro-fluidic manipulations with transformative potential for assembly,micro-manufacturing,the life sciences,robotics and optohydraulically actuated micro-factories.

关键词： manipulation fluid assembly

Biotransformation of ethylene glycol by engineered Escherichia coli

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Synthetic and systems Biotechnology 2024年第3期9卷 531-539页

作者： Wenlong Yan Xinhua Qi Zhibei Cao Mingdong Yao Mingzhu Ding Yingjin Yuan Frontiers Science center for Synthetic biology and Key Laboratory of systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China Frontiers Research Institute for Synthetic biology Tianjin UniversityTianjin300072China

There has been extensive research on the biological recycling of PET waste to address the issue of plastic waste pollution,with ethylene glycol(EG)being one of the main components recovered from this ***,finding ways to convert PET monomer EG into high-value products is crucial for effective PET waste *** this study,we successfully engineered Escherichia coli to utilize EG and produce glycolic acid(GA),expecting to facilitate the biological recycling of PET *** engineered ***,able to utilize 10 g/L EG to produce 1.38 g/L GA within 96 h,was initially ***,strategies based on overexpression of key enzymes and knock-out of the competing pathways are employed to enhance EG utilization along with GA *** engineered ***,characterized by the highest GA production titer and substrate conversion rate,was *** GA titer increased to 5.1 g/L with a yield of 0.75 g/g EG,which is the highest level in the shake flake *** level analysis and metabolomic analysis were then conducted,revealing that overexpression of key enzymes and knock-out of the competing pathways improved the metabolic flow in the EG *** improved metabolic flow also leads to accelerated synthesis and metabolism of amino acids.

关键词： PET biological recycling Ethylene glycol utilization Glycolic acid production Escherichia coli Synthetic biology Metabolomics analysis

Enhancing whole yeast genome rearrangements through multiple LoxPsym sequences

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Science China(Life Sciences) 2024年第9期67卷 2045-2047页

作者： Bing-Zhi Li Ying-Jin Yuan Frontiers Science center for Synthetic biology and Key Laboratory of systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China Frontiers Research Institute for Synthetic biology Tianjin UniversityTianjin 300072China

Genomic rearrangements play a significant role in disease,evolution,and tumorigenesis(Mani and Chinnaiyan,2010).While single nucleotide polymorphisms(SNPs)and small insertions/deletions contribute substantially to gen... 详细信息

关键词： insertion sequences