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Self-replicating digital data storage with synthetic chromosomes

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National Science Review 2021年第7期8卷 66-67页

作者： Xinyu Lu Tom Ellis Imperial College centre for synthetic biology Imperial College London department of bioengineering Imperial College London Wellcome Trust Sanger Institute

With the rapid development of the Internet and computational technologies, the exponential growth of digital data is beginning to overwhelm existing storage device capacities, driving an unprecedented demand for new data storage media. DNA, a natural genetic information storage system, has been proposed as a promising alternative[1]. Compared with traditional siliconbased storage, DNA-based storage hasmany advantages—incredible density,

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synthetic biology in the UK-An outline of plans and progress

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synthetic and Systems Biotechnology 2016年第4期1卷 243-257页

作者： L.J.Clarke R.I.Kitney UK synthetic biology Leadership Council UK department of bioengineering Imperial CollegeUK Faculty of Life Sciences University of ManchesterUK BionerG UK EPSRC National centre for synthetic biology and Innovation UK Institute of Systems and synthetic biology UK BioMedical Systems Engineering Imperial CollegeUK BioMedical Systems EngineeringImperial CollegeUK

synthetic biology is capable of delivering new solutions to key challenges spanning the bioeconomy,both nationally and *** this significant potential and the associated need to facilitate its translation and commercialisation the UK government commissioned the production of a national synthetic biology Roadmap in 2011,and subsequently provided crucial support to assist its *** infrastructural investments have been made,and important strides made towards the development of an effectively connected community of practitioners and interest groups.A number of synthetic biology Research centres,DNA Synthesis Foundries,a centre for Doctoral Training,and an Innovation Knowledge centre have been established,creating a nationally distributed and integrated network of complementary facilities and *** UK synthetic biology Leadership Council published a UK synthetic biology Strategic Plan in 2016,increasing focus on the processes of translation and *** 50 start-ups,SMEs and larger companies are actively engaged in synthetic biology in the UK,and inward investments are starting to *** these initiatives provide an important foundation for stimulating innovation,actively contributing to international research and development partnerships,and helping deliver useful benefits from synthetic biology in response to local and global needs and challenges.

关键词： synthetic biology Engineering biology Biodesign Roadmap Responsible Research and Innovation(RRI) Innovation and Knowledge centre(IKC) synthetic biology Leadership Council(SBLC) Bioeconomy

Benchmarking two Saccharomyces cerevisiae laboratory strains for growth and transcriptional response to methanol

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synthetic and Systems Biotechnology 2019年第4期4卷 180-188页

作者： Monica I.Espinosa Thomas C.Williams Isak S.Pretorius Ian T.Paulsen ARC centre of Excellence in synthetic biology Department of Molecular SciencesMacquarie UniversityNSWAustralia CSIRO synthetic biology Future Science Platform CanberraACT2601Australia

One-carbon compounds,such as methanol,are becoming potential alternatives to sugars as feedstocks for the biological production of chemicals,fuels,foods,and *** biological production often requires extensive genetic manipulation of a microbial host strain,making well-characterised and geneticallytractable model organisms like the yeast Saccharomyces cerevisiae attractive targets for the engineering of methylotrophic *** strains S288C and *** are the two best-characterised and most widely used hosts for yeast synthetic biology and metabolic engineering,yet they have unpredictable metabolic phenotypes related to their many genomic *** therefore sought to benchmark these two strains as potential hosts for engineered methylotrophic metabolism by comparing their growth and transcriptomic responses to *** had improved growth in the presence of methanol relative to the S288C derivative *** *** transcriptome also had a specific and relevant response to methanol that was either absent or less pronounced in the BY4741 *** response included up-regulation of genes associated with mitochondrial and peroxisomal metabolism,alcohol and formate dehydrogenation,glutathione metabolism,and the global transcriptional regulator of metabolism ***-expression of MIG3 enabled improved growth in the presence of methanol,suggesting that MIG3 is a mediator of the superior *** strain *** was therefore identified as a superior strain for the future development of synthetic methylotrophy in ***.

关键词： Yeast Methylotrophy synthetic biology Metabolic engineering MIG3 Methanol

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

Facile purification and immobilization of organophosphorus hydrolase on protein-inorganic hybrid phosphate nanosheets

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Chinese Journal of Chemical Engineering 2023年第4期56卷 119-125页

作者： Zhenfu Wang Jie Gao Qinghong Shi Xiaoyan Dong 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

Oriented immobilization of enzymes helps to maintain their native structure and proper orientation for high-performance engineering to meet extensive biocatalysis ***,the supporting materials used for orientated immobilization are usually costly or complicated in preparation,affecting their practical *** this work,a facile purification and immobilization method was proposed for enzyme immobilization based on organic-inorganic hybrid calcium phosphate nanocrystal(Ca Ps)induced by Cu^(2+) modified bovine serum albumin(BSA-Cu).Then,the as-prepared hybrid calcium phosphate nanosheet,BSA-Cu@Ca Ps,was utilized for one-pot purification and immobilization of His-tagged organophosphorus hydrolase(OPH)by metal-affinity binding to the incorporated ***-Cu@Ca PsOPH exhibited enhanced p H stability and thermal stability compared to the free ***,BSA-Cu@Ca Ps-OPH could retain more than 75%and 56%of initial activity after reuse 5 and 10 times,*** results demonstrated that this facile strategy was promising for the effective biodegradation of organophosphorus pesticides with the immobilized enzyme.

关键词： Calcium phosphate nanocrystal(CaPs) Biomimetic mineralization Organophosphorus hydrolase(OPH) Oriented immobilization Hydrolysis Methyl parathion

a-Synuclein: A fusion chaperone significantly boosting the enzymaticperformance of PET hydrolase

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Chinese Journal of Chemical Engineering 2023年第12期64卷 18-25页

作者： Renwen Tian 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

Extensive use of polyethylene terephthalate (PET) has brought about global environmental problems. Arecently reported PET hydrolase (PETase) discovered from Ideonella sakaiensis showed high potentialfor degrading PET at moderate temperatures, but its activity and stability need further improvementfor practical applications. Herein, we proposed to use a-synuclein (aS) as a fusion chaperone and createdsix PETase-aS fusion enzymes with linkers of different types and lengths. All the fusion enzymes exhibited improved enzymatic performance, presenting 1.5 to 2.6-fold higher activity towards bis-2(hydroxyethyl) terephthalate than PETase, as well as significantly increased stabilities. Fluorescencespectroscopy indicated that the chaperone fusion tightened the overall conformation and resulted inthe opening of the substrate binding pocket, which led to the improved thermal stability and catalyticactivity of the fusion enzymes. Remarkably, one of the fusion proteins, PETase-[(GS)(EK)]10-aS, showed3.2 to 5.1 times higher PET degradation capability than PETase. The significantly boosted PET degradationperformance was not only attributed to the enhanced enzymatic activity and stability, but also possiblydue to the binding affinity of the fused aS domain for PET. These findings demonstrated that aS was aneffective fusion chaperone for significantly enhancing the enzymatic performance of PETase.

关键词： PET hydrolase a-Synuclein Fusion enzyme Stability Pollution Degradation

Multiple effects of polydopamine nanoparticles on Cu^(2+)-mediated Alzheimer's β-amyloid aggregation

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Chinese Journal of Chemical Engineering 2023年第2期54卷 144-152页

作者： Xueqing Chen Weiqun Gao Yan Sun Xiaoyan Dong 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

Deposition of β-amyloid protein(Aβ) is the main hallmark of Alzheimer's disease(AD), and it has been well recognized that Cu^(2+)-mediated Aβ aggregation plays a crucial role in AD pathological ***^(2+)binding to Aβ can promote the production of reactive oxygen species(ROS) through Fenton-like reactions and produce more toxic Aβ-Cu^(2+)species under Cu^(2+)stimulation. Thus, the development of nanomaterials that can inhibit Cu^(2+)-mediated Aβ aggregation and degrade Aβ-Cu^(2+)complexes is considered an effective strategy for the prevention and treatment of AD. In this study, polydopamine nanoparticles(PDA NPs) were prepared and the results reveal that PDA NPs potently inhibit Cu^(2+)-mediated Aβaggregation and effectively reduce the formation of Aβ-Cu^(2+)complexes. In vitro experiments show that PDA NPs efficiently eliminate ROS generation catalyzed by Cu^(2+)or Aβ-Cu^(2+)complexes, thus rescuing cultured cells by reducing intracellular ROS levels. More importantly, PDA NPs can depolymerize Aβ-Cu^(2+)complexes, and the degradation of Aβ-Cu^(2+)complexes is promoted by near-infrared light irradiation due to their high photothermal conversion ability. In vivo studies reveal that PDA NPs significantly reduce the deposition of Aβ plaques in the presence of Cu^(2+)and extend the lifespan of AD nematodes from 11 to 14 d. Thus, the PDA NPs developed herein are multifunctional against Cu^(2+)-mediated Aβ aggregation for the potential prevention and treatment of AD.

关键词： Protein Aggregation Nanoparticles Photothermal therapy Reactive oxygen species Cu^(2+)chelator

Chiral LVFFARK enantioselectively inhibits amyloid-β protein fibrillogenesis

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Chinese Journal of Chemical Engineering 2022年第8期35卷 227-235页

作者： Wei Liu Xueting Sun Xiaoyan Dong 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

The modulation of protein aggregation is involved not only in biochemical engineering processes,but also in in vivo biological events such as Alzheimer's disease(AD)that features amyloid-βprotein(Aβ)*** by the different pharmacological efficacy of enantiomers,taking heptapeptide LVFFARK(LK7)as an example,herein the chiral influence of peptide inhibitors on Aβfibrillogenesis and cytotoxicity was investigated by extensive biophysical and biological *** was intriguing to find that although both LLK7 and D-LK7 could inhibit Aβaggregation in a concentration-dependent manner,it was the D-enan-tiomer that exhibited chirality preference and selectivity for modulation of Aβ*** com-pared with L-LK7 at the same conditions,D-LK7 showed significantly enhanced potency on suppressing cross-βsheet formation,fibrillar Aβaggregates deposition,Aβconformational transition,and Aβ-triggered neurotoxicity on cultured *** instance,***7 and D-LK7 rescued cells by increasing cell via-bility from 60%to 62%and 84%at 100μmolL^(-1),*** chiral discrimination of L-LK7 and D-LK7 was further validated by the different elimination efficiency on amyloid accumulation in AD model *** is considered that the higher binding affinity of D-LK7 to Aβmonomers than that of L LK7 resulted in the stronger inhibition *** work provided new insights into understanding chiral-ity in the interaction with Aβand the consequent inhibitory effect,and would contribute to the design of anti-amyloid agents.

关键词： Alzheimer’s disease Amyloid-b protein Protein aggregation Chirality Inhibitor Heptapeptide

A survey of sub-inhibitory concentrations of antibiotics in the environment

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Journal of Environmental Sciences 2021年第1期33卷 21-27页

作者： Louise K.M.Chow Timothy M.Ghaly Michael R.Gillings department of Biological Sciences Macquarie UniversityNSW 2109Australia ARC centre of Excellence in synthetic biology Macquarie UniversityNSW 2109Australia

Antibiotics are poorly metabolized,and can enter the environment via human waste streams,agricultural run-off and pharmaceutical *** consequently expect to see a concentration gradient of antibiotic compounds radiating from areas of human *** antibiotics should be thought of as pollutants,as they can accumulate,and have biological *** antibiotic pollutants can increase rates of mutation and lateral transfer events,and continue to exert selection pressure even at sub-inhibitory ***,we conducted a literature survey on environmental concentrations of *** collated 887 data points from 40 peer-reviewed *** then determined whether these concentrations were biologically relevant by comparing them to their minimum selective concentrations,usually defined as between 1/4 and 1/230 of the minimum inhibitory *** concentrations of antibiotics surveyed often fall into this *** general,the antibiotic concentrations recorded in aquatic and sediment samples were *** findings indicate that environmental concentrations of antibiotics are likely to be influencing microbial ecology,and to be driving the selection of antibiotic resistant bacteria.

关键词： Antimicrobial Pollution Evolution Microorganism Environment Antibiotic resistance