Biotechnology articles within Nature Chemistry

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  • Article |

    Proteins have the potential to serve as powerful scaffolds that control the catalytic activity and selectivity of organometallic centres; however, new methods are needed to optimize artificial metalloenzymes. Now, an efficient approach for evolving the activity and selectivity of artificial metalloenzymes has been demonstrated using dirhodium cyclopropanases. This approach does not require structural or mechanistic data to guide mutagenesis.

    • Hao Yang
    • , Alan M. Swartz
    •  & Jared C. Lewis

  • Article |

    Biomaterials that respond to precise combinations of environmental cues represent an important technology for tissue engineering and next-generation drug delivery systems. Now, a modular framework to programme material degradation following Boolean logic has been demonstrated by specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within hydrogel cross-linkers.

    • Barry A. Badeau
    • , Michael P. Comerford
    •  & Cole A. DeForest

  • Article |

    Peptides derived from non-ribosomal peptide synthetases (NRPS) are an important class of pharmaceutically relevant drugs. However, no general rules for the modification of NRPS or the generation of artificial NRPS are known. Now, a new strategy for the modification of NRPS has been developed that uses defined exchange units that are fused at specific positions connecting the condensation and adenylation domains.

    • Kenan A. J. Bozhüyük
    • , Florian Fleischhacker
    •  & Helge B. Bode

  • News & Views |

    DNA double helical structures are supramolecular assemblies that are typically held together by classical Watson–Crick pairing. Now, nucleotide chelation of silver ions supports an extended silver–DNA hybrid duplex featuring an uninterrupted silver array.

    • Pascal Auffinger
    •  & Eric Ennifar

  • Perspective |

    Glucose-responsive insulin is a therapeutic that modulates its potency, concentration or dosing relative to a patient’s dynamic glucose concentration. This Perspective summarizes some of the recent accomplishments in this field as well as discussing new computational algorithms that may aid in the development of such therapeutics.

    • Naveed A. Bakh
    • , Abel B. Cortinas
    •  & Michael S. Strano

  • News & Views |

    Intracellular protein delivery has been a major challenge in the field of cell biology for decades. Engineering such delivery is a key step in the development of protein- and antibody-based therapeutics. Now, two different approaches that enable the delivery of antibodies and antibody fragments into the cytosol have been developed.

    • Macarena Sánchez-Navarro
    • , Meritxell Teixidó
    •  & Ernest Giralt

  • Article |

    Delivery of antibodies into living cells enables the labelling and manipulation of intracellular antigens; however, transporting antibodies into the cytosol in a functional state is difficult. Now, a modular strategy for creating cell-permeable nanobodies capable of targeting intracellular antigens has been developed. The cell-permeable nanobodies are formed by site-specific attachment of cyclic arginine-rich cell-penetrating peptides to camelid-derived single-chain antibody fragments.

    • Henry D. Herce
    • , Dominik Schumacher
    •  & Christian P. R. Hackenberger

  • Article |

    Modular hybridization probes (M-Probes) have been developed that enable sequence-selective binding of complex nucleic acid targets. The M-probes can target sequences that: are hypervariable at prescribed loci, are long continuous sequences of over 500 nucleotides, or contain repetitive sequences. A hybrid-capture assay using the M-probes was developed that was capable of determining the exact triplet repeat expansion number in the Huntington's gene from genomic DNA.

    • Juexiao Sherry Wang
    • , Yan Helen Yan
    •  & David Yu Zhang

  • Article |

    A metallo–DNA hybrid nanowire composed only of silver-mediated base pairs has been prepared and its crystal structure resolved by X-ray diffraction. The nanowire, which is 2 nm wide and whose length reaches the μm to mm scale, holds silver ions into uninterrupted one-dimensional arrays along the DNA helical axis.

    • Jiro Kondo
    • , Yoshinari Tada
    •  & Yoshiyuki Tanaka

  • Article |

    Controlling liposome shape, arrangement and dynamics is important for biophysical studies and synthetic biology applications. Now, using a family of reconfigurable DNA nanocages as templates, spherical, tubular, toroidal and helical liposomes with predefined geometry have been produced. DNA-guided membrane fusion and bending is also demonstrated.

    • Zhao Zhang
    • , Yang Yang
    •  & Chenxiang Lin

  • Article |

    The trapping of antibodies in endosomes often limits their use for intracellular targeting. Now, a single amino acid substitution on a spider-venom peptide has been shown to attenuate the cell membrane lytic activity and enables the selective rupturing of endosomal membranes. The peptide can be used to facilitate the escape of antibodies from endosomes into the cytosol.

    • Misao Akishiba
    • , Toshihide Takeuchi
    •  & Shiroh Futaki

  • Article |

    Abiotic hydrogel polymer nanoparticles with affinity for a key vascular endothelial growth factor (VEGF165) have now been developed. This high-protein affinity was engineered by carefully controlling the amount and the substitution pattern of sulfated N-acetylglucosamines and the inclusion of a hydrophobic group in the monomer.

    • Hiroyuki Koide
    • , Keiichi Yoshimatsu
    •  & Kenneth J. Shea

  • News & Views |

    The targeted release of bioactive molecules to diseased tissues has the potential to improve therapeutic efficacy, but not all drugs contain a free functional group that can be easily attached to an antibody. Now, a linker technology has been developed to enable the traceless release of tertiary and heteroaryl amine-containing drugs.

    • Tiago Rodrigues
    •  & Gonçalo J. L. Bernardes

  • Article |

    The assembly of transmembrane barrels formed from short synthetic peptides has not been previously demonstrated. Now, a transmembrane pore has been fabricated via the self-assembly of peptides. The 35-amino-acid α-helical peptides are based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza.

    • Kozhinjampara R. Mahendran
    • , Ai Niitsu
    •  & Hagan Bayley

  • Article |

    Genetic circuits are important for synthetic biology, biochemistry and bioengineering. Now, the encapsulation of genetic circuits into liposomes has been shown to enable a more modular design, the selective isolation of reactions from the environment and from each other, and the hierarchical assembly of reaction products.

    • Katarzyna P. Adamala
    • , Daniel A. Martin-Alarcon
    •  & Edward S. Boyden

  • Article |

    Many drugs contain tertiary and heteroaryl amines; however, these functional groups are difficult to reversibly crosslink to a carrier protein. Now, a method for conjugating anticancer and antibiotic drugs to antibodies via a quaternary ammonium salt has been developed. Cleavage of the linker results in the traceless release of the free drug and subsequent therapeutic activity.

    • Leanna R. Staben
    • , Stefan G. Koenig
    •  & Thomas H. Pillow

  • Article |

    A protein-only redox film inspired by the architecture of bacterial electroactive biofilms has been developed. The film is formed using a rubredoxin–prion domain chimeric protein. The prion domains self-assemble into fibres that are decorated with rubredoxin. This results in highly organized films, able to transport electrons over several microns, and wire enzymes to electrodes.

    • Lucie Altamura
    • , Christophe Horvath
    •  & Vincent Forge

  • Article |

    A mirror-image polymerase—a version of African swine fever virus polymerase X made from D-amino acids—has now been chemically synthesized. This polymerase can catalyse template-directed L-DNA replication and transcription from L-DNA into L-RNA. These reactions represent two key steps in the central dogma of molecular biology—but demonstrated using the opposite chirality.

    • Zimou Wang
    • , Weiliang Xu
    •  & Ting F. Zhu

  • Article |

    Naturally occurring DNA polymerases can amplify DNA efficiently via PCR, but they cannot utilize C2′-modified substrates to make non-natural nucleic acids. Such C2′-modified nucleic acids are of interest as they are resistant to nucleases. Now, a Stoffel fragment DNA polymerase has been evolved to transcribe C2′-modified DNA from a DNA template, reverse transcribe C2′-modified DNA back into DNA, and PCR-amplify C2′-modified DNA.

    • Tingjian Chen
    • , Narupat Hongdilokkul
    •  & Floyd E. Romesberg

  • News & Views |

    Expanding the range of amino acids polymerizable by ribosomes could enable new functionalities to be added to polypeptides. Now, the genetic code has been reprogrammed using a reconstituted in vitro translation system to enable synthesis of unnatural peptides with unmatched flexibility.

    • Michael C. Jewett
    •  & Vincent Noireaux

  • Article |

    The repertoire of amino acids available for ribosomal peptide synthesis is limited by the genetic code. Now, a method to reduce the redundancy of codons has been developed based on the artificial division of codon boxes. This method enables non-proteinogenic amino acids to be included in peptides without sacrificing proteinogenic ones.

    • Yoshihiko Iwane
    • , Azusa Hitomi
    •  & Hiroaki Suga

  • Perspective |

    Antibody–drug conjugates have shown considerable promise for treating disease. However, in order to deliver their full potential, sophisticated site-specific conjugation technologies are needed. This Perspective provides an overview of the different methods used for the site-specific attachment of cytotoxic agents to antibodies.

    • Vijay Chudasama
    • , Antoine Maruani
    •  & Stephen Caddick

  • Article |

    The encapsulation and stabilization of an oxygen tolerant [NiFe]-hydrogenase, sequestered within the bacteriophage P22 capsid, has now been achieved through a directed self-assembly process. Probing the catalytic activity and infrared spectroscopic signatures of the bio-inspired assembly shows that the capsid provides stability and protection to the hydrogenase cargo.

    • Paul C. Jordan
    • , Dustin P. Patterson
    •  & Trevor Douglas

  • Article |

    Selective reaction of one C–H bond among many in complex organic molecules is a grand challenge for organic chemistry. Here, starting from an enzyme that oxidizes two positions in a steroid without bias, laboratory evolution is used to prepare mutants that can regio- and stereoselectively oxidize either position.

    • Sabrina Kille
    • , Felipe E. Zilly
    •  & Manfred T. Reetz

  • Article |

    The impact of photo-damage on natural photosynthetic systems is lessened through their autonomous self-repair, and now a synthetic photoelectrochemical complex that mimics this behaviour has been developed. It is shown that a series of regeneration steps, driven by chemical signalling, increases the photo-conversion efficiency of the system and extends its lifetime indefinitely.

    • Moon-Ho Ham
    • , Jong Hyun Choi
    •  & Michael S. Strano

  • News & Views |

    The iron active sites of enzymes routinely cleave strong C–H bonds, but synthetic complexes have so far been much slower and less efficient. Now, the reactivity of a biomimetic diiron complex has been dramatically enhanced by converting its oxo bridge into a terminal ligand, and its iron centre from low spin to high spin.

    • Sason Shaik

  • News & Views |

    Among the wide variety of synthetic processes that chemists have developed, only a few can be carried out under physiological conditions. A condensation reaction that is controlled by the constituents of cells has led to the formation of nanostructures within living cells.

    • Bing Xu

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