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Material-engineered bioartificial microorganisms enabling efficient scavenging of waterborne viruses
The material-based evolution of organisms has attracted broad interdisciplinary interest, however, the fabrication of material-integrated organelles remains inadequately exploited. Here the authors engineer a bioartificial organism by integrating a semiartificial and specific virus-scavenging organelle to scavenge pathogenic waterborne viruses.
- Huixin Li
- , Yanpeng Xu
- & Ruikang Tang
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Article
| Open Access
Discovery and rational engineering of PET hydrolase with both mesophilic and thermophilic PET hydrolase properties
Extensive research efforts have been directed towards the development of PET hydrolases with improved activity, but template enzymes used are limited. Here, the authors report a PET hydrolase from Cryptosporangium aurantiacum (CaPETase) that exhibits high thermostability and PET degradation activity at ambient temperatures and determine its crystal structure.
- Hwaseok Hong
- , Dongwoo Ki
- & Kyung-Jin Kim
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| Open Access
Crystal structures of herbicide-detoxifying esterase reveal a lid loop affecting substrate binding and activity
The esterase SulE, which detoxifies and hydrolyses a variety of sulfonylurea herbicides, is increasingly of interest in efforts to eliminate environmental contamination of sulfonylurea herbicides and engineer herbicide-tolerant crops. Here, the SulE is structurally and mechanistically characterised.
- Bin Liu
- , Weiwu Wang
- & Jian He
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| Open Access
Discovery and mechanism-guided engineering of BHET hydrolases for improved PET recycling and upcycling
The degradation of PET using PETase enzymes has great potential but can face problems with incomplete degradation. Here, the authors identified two BHETases from the environment and engineered them to improve their hydrolysis efficiency for applications in dual-enzyme PET recycling and tandem chemical-enzymatic PET upcycling systems.
- Anni Li
- , Yijie Sheng
- & He Huang
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| Open Access
Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase
Diterpene synthase VenA catalyses the synthesis of venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. Here, the authors report crystal structures of apo- and holo-VenA, provide mechanistic insights into its substrate selectivity and promiscuity, and engineer VenA into a sesterterpene synthase.
- Zhong Li
- , Lilan Zhang
- & Shengying Li
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Article
| Open Access
An unnatural enzyme with endonuclease activity towards small non-coding RNAs
Endonucleases play crucial roles in various biological processes but endonucleases that target small non-coding RNAs have not been reported. Here, the authors combined the metal binding non-canonical amino acid BpyAla and a high affinity binder to engineer a catalyst that degrades small non-coding RNAs.
- Noreen Ahmed
- , Nadine Ahmed
- & John Paul Pezacki
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Green synthesis of stable hybrid biocatalyst using a hydrogen-bonded, π-π-stacking supramolecular assembly for electrochemical immunosensor
Integration of nanomaterials and enzymes has potential in the development of robust biocatalysts, but preparation can still be technically challenging. Here, the authors report the preparation of a hydrogen-bonded organic framework biocatalyst and its use as an immunosensor.
- Wei Huang
- , Haitao Yuan
- & Gangfeng Ouyang
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Article
| Open Access
Discovery of extended product structural space of the fungal dioxygenase AsqJ
The fungal dioxygenase AsqJ catalyses the conversion of benzo[1,4]diazepine-2,5-diones into quinolone antibiotics, and can also catalyse the production of quinazolinones. Here, the authors perform comprehensive substrate promiscuity mapping of AsqJ revealing its large tolerance towards various substrates, giving biocatalytic access to a plethora of biomedically valuable heterocyclic frameworks.
- Manuel Einsiedler
- & Tobias A. M. Gulder
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| Open Access
Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules
Plastic-degrading enzymes can be utilized for plastic recycling. Here, QM/MM molecular dynamics and experimental Michaelis–Menten kinetics provide insight into PETase/MHTase activities of the lipase B from Candida antartica.
- Katarzyna Świderek
- , Susana Velasco-Lozano
- & Vicent Moliner
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Article
| Open Access
Multi-compartmental MOF microreactors derived from Pickering double emulsions for chemo-enzymatic cascade catalysis
The cell-like structures and the ability of assembling catalytic species are interesting features of bioinspired multicompartment architectures but it remains a challenge to build them. Here, the authors describe a Pickering double emulsion-directed interfacial synthesis to fabricate multi-compartmented metal-organic framework microreactors. The cell-like structures and the ability of assembling catalytic species are interesting features of bioinspired multicompartment architectures but it remains a challenge to build them. Here, the authors describe a Pickering double emulsion-directed interfacial synthesis to fabricate multi-compartmented metal-organic framework microreactors.
- Danping Tian
- , Ruipeng Hao
- & Hengquan Yang
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Article
| Open Access
Hydrogenase-based oxidative biocatalysis without oxygen
Currently, NADH oxidases, (NOXs) are the standard regeneration, systems for oxidized nicotinamides but their dependency on O2 limits, their application at industrial scale. Here, the authors established an O2-free system, based on [NiFe] hydrogenase that, regenerates oxidized nicotinamides.
- Ammar Al-Shameri
- , Dominik L. Siebert
- & Volker Sieber
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| Open Access
Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis
Fungal siderophores are biosynthesised by nonribosomal peptide synthetases (NRPSs) with highly unusual domain architectures. Here, the authors characterise cryptic programming events occurring within SidC NRPS, responsible for ferricrocin biosynthesis in Aspergillus nidulans.
- Matthew Jenner
- , Yang Hai
- & Yi Tang
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| Open Access
Adaptable graphitic C6N6-based copper single-atom catalyst for intelligent biosensing
Catalysts with multiple and modulable reaction pathways are promising but generally hampered by inconsistent reaction conditions and negative internal interferences. Herein, the authors report an adaptable graphitic C6N6-based copper singleatom catalyst
- Qing Hong
- , Hong Yang
- & Yuanjian Zhang
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Article
| Open Access
Engineering a new-to-nature cascade for phosphate-dependent formate to formaldehyde conversion in vitro and in vivo
A key step in the assimilation of formate is its reduction into formaldehyde. Here, the authors develop a two-enzyme route in which formate is activated into formyl phosphate and reduced by NAD(P)H into formaldehyde and confirm its functionality in vitro and in vivo.
- Maren Nattermann
- , Sebastian Wenk
- & Tobias J. Erb
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Article
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Engineered repeat proteins as scaffolds to assemble multi-enzyme systems for efficient cell-free biosynthesis
Multi-enzymatic cascades benefit from precise nanometric organization but achieving this using available scaffolds is challenging. Here the authors present strategy for organizing multienzymatic systems using a protein scaffold based on TRAP domains, and demonstrate improved catalytic output.
- Alba Ledesma-Fernandez
- , Susana Velasco-Lozano
- & Aitziber L. Cortajarena
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| Open Access
N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry
A biosynthetic enzyme that mediates ligand-protein NOS chemistry allowing addition and decarboxylation alongside noncanonical FAD-dependent reactions to implement the N-formimidoylation/-iminoacetylation modification in aminoglycosides was uncovered.
- Yung-Lin Wang
- , Chin-Yuan Chang
- & Tsung-Lin Li
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Article
| Open Access
Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity
Low activity currently prevents the wider use of DNA enzymes (DNAzymes). Here the authors report the chemical evolution of a DNAzyme with high catalytic activity under near physiological conditions: the enzyme achieves ~65 turnovers in 30 minutes.
- Kim Nguyen
- , Turnee N. Malik
- & John C. Chaput
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| Open Access
A selective and atom-economic rearrangement of uridine by cascade biocatalysis for production of pseudouridine
Pseudouridine (Ψ), the C-nucleoside isomer of uridine, and its 1-N-methyl derivative, are incorporated in mRNA vaccines and essential for their efficiency, but difficult to synthetically access. Here, the authors report on selective and atom-economic 1N-5C rearrangement of β-d-ribosyl on uracil to obtain Ψ from unprotected U in quantitative yield
- Martin Pfeiffer
- , Andrej Ribar
- & Bernd Nidetzky
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| Open Access
Active and stable alcohol dehydrogenase-assembled hydrogels via synergistic bridging of triazoles and metal ions
Biocatalysis using immobilized enzymes is increasingly replacing traditional methods of manufacturing fine chemicals but heir industrial applications are limited by the low specific activity and poor stability. Here, the authors report a feasible strategy utilizing the synergistic bridging of triazoles and metal ions to induce the formation of porous enzyme-assembled hydrogels with increased activity.
- Qiang Chen
- , Ge Qu
- & Guangsheng Luo
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Article
| Open Access
Bioelectrocatalysis with a palladium membrane reactor
Enzymatic catalysis requires cofactors such as NAD(P)H, whose regeneration is currently accomplished via secondary enzymes or electrolytic cell. Here, the authors report an electrochemical method of cofactors regeneration without supporting enzymes or mediators, nor formation of NAD2 dimers.
- Aiko Kurimoto
- , Seyed A. Nasseri
- & Curtis P. Berlinguette
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Article
| Open Access
Self assembling nanoparticle enzyme clusters provide access to substrate channeling in multienzymatic cascades
Channeling between enzymes is a uniquely nanoscale phenomenon that can improve multienzymatic reaction rates. Here, the authors demonstrate that multistep enzyme cascades can self-assemble with nanoparticles into nanoclusters that access channeling and improve the underlying catalytic flux by several fold.
- Joyce C. Breger
- , James N. Vranish
- & Igor L. Medintz
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| Open Access
Unnatural activities and mechanistic insights of cytochrome P450 PikC gained from site-specific mutagenesis by non-canonical amino acids
The 20 proteinogenic amino acids cannot always satisfy the requirements of protein engineering. Here, the authors practice semi-rational non-canonical amino acid mutagenesis for a cytochrome P450 enzyme, leading to unnatural activities and significant mechanistic insights.
- Yunjun Pan
- , Guobang Li
- & Shengying Li
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Article
| Open Access
The structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex
The formation of the mitotic checkpoint complex requires an intricate spatial coordination amongst the proteins Bub1, Mad1, Cdc20, and Mad2. Chen et al show that a structural flexibility in Mad1 plays an essential role in achieving this coordination.
- Chu Chen
- , Valentina Piano
- & Ajit P. Joglekar
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| Open Access
C–N bond formation by a polyketide synthase
Polyketide synthases (PKSs) usually form C–C bonds in natural products biosynthesis. Here, the authors present cryo-EM structures of a PKS in complex with products, which provides insight into the mechanism of the unexpected C–N bond formation.
- Jialiang Wang
- , Xiaojie Wang
- & Jingdan Liang
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Article
| Open Access
Visible light-exposed lignin facilitates cellulose solubilization by lytic polysaccharide monooxygenases
Degradation of plant biomass, comprised of cellulose and polyaromatic lignin, is promoted by light. Here, the authors show that light promotes lignin-catalyzed generation of hydrogen peroxide, which is used by redox enzymes to degrade cellulose.
- Eirik G. Kommedal
- , Camilla F. Angeltveit
- & Vincent G. H. Eijsink
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Emergence of a proton exchange-based isomerization and lactonization mechanism in the plant coumarin synthase COSY
Plant biosynthetic enzymes rapidly evolve to catalyze specialized reactions. Here, the authors present the crystal structure and mechanism of COSY, the enzyme involved in coumarin biosynthesis of the BAHD-acyltransferase family that catalyzes an intramolecular acyl transfer reaction through a proton exchange mechanism.
- Colin Y. Kim
- , Andrew J. Mitchell
- & Jing-Ke Weng
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Regioselective protein oxidative cleavage enabled by enzyme-like recognition of an inorganic metal oxo cluster ligand
Metal-catalysed oxidation of proteins varies in selectivity and depends on the surface residues to direct the reaction. Here, the authors use polyoxometalate clusters as inorganic ligands for Cu ions, enabling the regioselective oxidative cleavage of a protein via reactive oxygen species in the vicinity of its binding sites.
- Shorok A. M. Abdelhameed
- , Francisco de Azambuja
- & Tatjana N. Parac-Vogt
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Manipulation of sterol homeostasis for the production of 24-epi-ergosterol in industrial yeast
Brassinolide (BL) is one of the most active compounds among phytohormone brassinosteroids (BRs) and can be used for plant growth and development regulation. Here, the authors report the construction of an artificial pathway in baker’s yeast for scalable production of 24-epi-ergosterol, a precursor for BL semi-synthesis.
- Yiqi Jiang
- , Zhijiao Sun
- & Lirong Yang
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Article
| Open Access
Structural analysis of an anthrol reductase inspires enantioselective synthesis of enantiopure hydroxycycloketones and β-halohydrins
Asymmetric reduction of prochiral ketones is challenging. Here, the authors identify and solve the structure of anthrol reductase CbAR, whose variant H162F can convert 1,3-cyclodiketones and α-haloacetophenones to the corresponding chiral alcohols.
- Xiaodong Hou
- , Huibin Xu
- & Yijian Rao
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Article
| Open Access
Deciphering the catalytic mechanism of superoxide dismutase activity of carbon dot nanozyme
Superoxide dismutase (SOD) nanozymes show mitigating effect on oxidative stress-related diseases, but are limited by their modest activity. Here, the authors report a carbon dot SOD nanozyme with catalytic activity matching natural enzymes and unveil its catalytic mechanism.
- Wenhui Gao
- , Jiuyang He
- & Xiyun Yan
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| Open Access
Sourcing thermotolerant poly(ethylene terephthalate) hydrolase scaffolds from natural diversity
Enzymes have potential for recycling plastics such as PET, a polyester used in textiles and single-use packaging. Here, the authors identify and characterize additional PET-active biocatalysts and expand the number and diversity of thermotolerant scaffolds for enzymatic PET deconstruction.
- Erika Erickson
- , Japheth E. Gado
- & John E. McGeehan
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| Open Access
Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles
Chiral heterocyclic compounds are privileged structures in medicinal chemistry. Here, the authors report an in silico strategy for the enzymatic synthesis of pharmaceutically significant chiral N- and O-heterocycles via Baldwin cyclization of hydroxy- and amino-substituted epoxides and oxetanes using epoxide hydrolase mutants.
- Jun-Kuan Li
- , Ge Qu
- & Zhoutong Sun
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| Open Access
Total enzymatic synthesis of cis-α-irone from a simple carbon source
Retrosynthetic pathway design using promiscuous enzymes can provide a solution to the biosynthetic production of natural products. Here, the authors design a pathway for the production of cis-α-irone with a promiscuous methyltransferase using structure-guided enzyme engineering strategies.
- Xixian Chen
- , Rehka T
- & Isabelle André
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| Open Access
Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin
High-crystallinity poly(ethylene terephthalate) is a major recycling challenge. Here, the authors show an engineered whole-cell biocatalyst showing adhesive hydrophobin and PETase on the surface of cells, for biodegradation of PET.
- Zhuozhi Chen
- , Rongdi Duan
- & Zefang Wang
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Article
| Open Access
Design and directed evolution of noncanonical β-stereoselective metalloglycosidases
Metallohydrolases are ubiquitous enzymes. Here the authors show the design and biochemical characterisation of metalloglycosidase by constructing a hydrolytically active Zn-binding site within a barrel-shaped outer membrane protein OmpF.
- Woo Jae Jeong
- & Woon Ju Song
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| Open Access
Solar-driven methanogenesis with ultrahigh selectivity by turning down H2 production at biotic-abiotic interface
While the combination of synthetic and biological systems offers an appealing strategy for solar-to-fuel conversion, such hybrid systems typically suffer from low selectivity. Here, authors integrate a bimetallic alloy with a CdS-containing methanogen for selective CO2 reduction to methane.
- Jie Ye
- , Chao Wang
- & Yujie Xiong
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Article
| Open Access
Endowing homodimeric carbamoyltransferase GdmN with iterative functions through structural characterization and mechanistic studies
Carbamoyltransferases are a class of enzymes catalyzing carbamoylation of primary and secondary metabolites. Here, the authors show the molecular structure of the ansamycin-modifying carbamoyltransferase GdmN and repurpose the enzyme for the iterative carbamoylation of ansamitocins.
- Jianhua Wei
- , Xuan Zhang
- & Linquan Bai
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Article
| Open Access
A universal glycoenzyme biosynthesis pipeline that enables efficient cell-free remodeling of glycans
Access to glycoenzymes for basic and applied research is limited by difficulties with their recombinant expression. Here, the authors describe a universal strategy for converting membrane-bound glycosyltransferases into water-soluble biocatalysts, which are expressed at high levels with retention of activity.
- Thapakorn Jaroentomeechai
- , Yong Hyun Kwon
- & Matthew P. DeLisa
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Article
| Open Access
Investigating lytic polysaccharide monooxygenase-assisted wood cell wall degradation with microsensors
It is important to understand the enzymatic degradation of wood biomass by lytic polysaccharide monooxygenase, however, disagreements about the co-substrate exist. Here, the authors use piezo-controlled hydrogen peroxide micro-sensors to demonstrate that even low levels of hydrogen peroxide support the enzymatic degradation of wood cell walls.
- Hucheng Chang
- , Neus Gacias Amengual
- & Roland Ludwig
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Article
| Open Access
Spheroplasts preparation boosts the catalytic potential of a squalene-hopene cyclase
Squalene-hopene cyclase are membrane-bound enzymes used to produce bioactive compounds at industrial scale. Here, the authors show squalene-hopene cyclase spheroplasts, obtained by removing the outer cell membrane, having a higher catalytic activity than the enzymes and the whole cells, and their cross-linking for recycling and reuse.
- Ana I. Benítez-Mateos
- , Andreas Schneider
- & Francesca Paradisi
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| Open Access
Metabolic pathway assembly using docking domains from type I cis-AT polyketide synthases
Assembly artificial pathway in design connecting media can increase biosynthetic efficiency, but the choice of connecting media is limited. Here, the authors develop a new protein assembly strategy using a pool of docking peptides from polyketide synthase and show its application in astaxanthin biosynthesis in E. coli.
- Xixi Sun
- , Yujie Yuan
- & Tian Ma
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| Open Access
Microbial biofilms as living photoconductors due to ultrafast electron transfer in cytochrome OmcS nanowires
Despite enormous potential of solar-driven biocatalysis, most living systems lack photoactive proteins and require toxic and expensive synthetic materials limiting the performance. Here, a class of natural photoconductors is demonstrated through sub-picosecond heme-to-heme electron transfer in bacteria-produced protein nanowires.
- Jens Neu
- , Catharine C. Shipps
- & Nikhil S. Malvankar
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| Open Access
Substrate multiplexed protein engineering facilitates promiscuous biocatalytic synthesis
Efficient engineering of enzymes for expanded substrate scope is currently challenging. Here, the authors develop simple principles of how to design and interpret Substrate Multiplexed Screening assays to guide protein engineering to enable activity improvements with simultaneously with multiple substrates.
- Allwin D. McDonald
- , Peyton M. Higgins
- & Andrew R. Buller
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| Open Access
Structural bases for aspartate recognition and polymerization efficiency of cyanobacterial cyanophycin synthetase
CphA1 catalyzes the synthesis of cyanophycin polypeptide consisting of equimolar amounts of aspartate and arginine as a fixed nitrogen reservoir in cyanobacteria. Here, the authors solve the cryo-EM structures of CphA1, revealing the aspartate binding mode and protein dynamics required for cyanophycin elongation.
- Takuya Miyakawa
- , Jian Yang
- & Masaru Tanokura
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| Open Access
Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis
Cocaine is a tropane alkaloid produced by Erythroxylum novogranatense. Here the authors identify two polyketide synthases involved in cocaine biosynthesis and provide insight into the parallel evolution of these enzymes in tropane alkaloids-producing plants.
- Tian Tian
- , Yong-Jiang Wang
- & Sheng-Xiong Huang
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Article
| Open Access
Flavin-enabled reductive and oxidative epoxide ring opening reactions
Epoxide ring opening reactions are important in both biological processes and synthetic applications. Here, the authors show that flavin cofactors can catalyze reductive and oxidative epoxide ring opening reactions and propose the underlying mechanisms.
- Bidhan Chandra De
- , Wenjun Zhang
- & Changsheng Zhang
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Article
| Open Access
Hydrogen-bonded organic framework biomimetic entrapment allowing non-native biocatalytic activity in enzyme
Heme units are immobilised in diverse heme enzymes for oxidation, and have been immobilised also in hydrogen-bonded organic frameworks. Here, the authors show the use of hydrogen-bonded organic framework to modulate the enzyme’s conformation and show different biofunction from the original.
- Guosheng Chen
- , Linjing Tong
- & Gangfeng Ouyang
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| Open Access
Single-atom nanozymes catalytically surpassing naturally occurring enzymes as sustained stitching for brain trauma
The catalytic activity of regenerable nanozymes is currently the bottle neck for their wider employment. Here, the authors report on single-atom nanozymes of RhN4, VN4, and Fe-Cu-N6 with higher catalytic activities than natural enzymes, and demonstrate the Rh/VN4 recyclability and scalp healing properties in bioactive sutures.
- Shaofang Zhang
- , Yonghui Li
- & Xiao-Dong Zhang
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| Open Access
Biocatalytic routes to stereo-divergent iridoids
Iridoid compounds are an important class of natural products. Here, the authors report on the discovery and engineering of nepetalactol-related short chain reductases and their application for the biosynthesis of nepetalactol or nepetalactone stereoisomers, as a versatile system for the production of the iridoid natural product scaffold.
- Néstor J. Hernández Lozada
- , Benke Hong
- & Sarah E. O’Connor
Structure of lasso peptide epimerase MslH reveals metal-dependent acid/base catalytic mechanism