Synthetic biology articles within Nature Chemistry

Featured

  • Article |

    A 335 base-pair gene encoding the green fluorescent protein iLOV and an epigenetically modified variant have now been assembled by click-DNA ligation of ten functionalized oligonucleotides. The resulting fully synthetic gene contained eight triazoles at the sites of chemical ligation, yet the synthetic gene was shown to be fully biocompatible in Escherichia coli.

    • Mikiembo Kukwikila
    • , Nittaya Gale
    •  & Ali Tavassoli

  • Article |

    The first demonstration of a protein designed entirely from first principles that binds a small-molecule cofactor in a precisely predetermined orientation has now been described. The design method utilizes a remote protein core that both anchors and predisposes a flexible binding site for the desired cofactor-binding geometry.

    • Nicholas F. Polizzi
    • , Yibing Wu
    •  & William F. DeGrado

  • Editorial |

    A range of mechanisms have evolved for communicating information across cell membranes, but designing synthetic analogues is far from trivial. A collection of articles in this issue discuss different methods of passing chemical information across lipid bilayers using artificial systems.

  • News & Views |

    Life has evolved elaborate means of communicating essential chemical information across cell membranes. Inspired by biology, two new artificial mechanisms have now been developed that use synthetic messenger molecules to relay chemical signals into or across lipid membranes.

    • Scott L. Cockroft

  • News & Views |

    Attempts to build lifelike synthetic protocells must consider extracellular influences in order to accurately reflect the behaviours and characteristics of real ecosystems. Now, this concept has been demonstrated by the synthesis of a community of protocells in which one cell type preys upon another.

    • Sheref S. Mansy

  • 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 |

    A generally applicable small-molecule switch for protein function in live cells has been developed based on selective protein protection using unnatural amino acid mutagenesis and a bioorthogonal deprotection via Staudinger reduction.

    • Ji Luo
    • , Qingyang Liu
    •  & Alexander Deiters

  • Article |

    A motif was identified in the scaffold of an (S)-selective transaminase that enables the asymmetric synthesis of bulky chiral amines. This motif is transferable to other enzymes with as low as 70% sequence identity. The biocatalysts developed show high stereoselectivity and their synthetic potential was confirmed in preparative scale synthesis.

    • Ioannis V. Pavlidis
    • , Martin S. Weiß
    •  & Uwe T. Bornscheuer

  • Article |

    Identifying a non-enzymatic method of replicating RNA for multiple cycles has been problematic because rapid strand reannealing outcompetes slow non-enzymatic template copying. Now, oligoarginine peptides have been shown to inhibit reannealing while still allowing short primers and activated monomers to bind to the template strand, facilitating the next round of template copying.

    • Tony Z. Jia
    • , Albert C. Fahrenbach
    •  & Jack W. Szostak

  • 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

  • Editorial |

    The modification of proteins with fluorophores, drugs and polymers is required for many applications, yet conjugation reactions often generate a heterogeneous mixture of products. A collection of articles in this issue focuses on methods to modify proteins in a site-selective manner.

  • Perspective |

    A wide range of different aqueous chemistries for the site-selective modification of proteins have been described over the past decade. This Perspective discusses the scope and potential of chemical site-selective protein-modification methods in the context of their biological and therapeutic applications.

    • Nikolaus Krall
    • , Filipa P. da Cruz
    •  & Gonçalo J. L. Bernardes

  • Perspective |

    Synthetic vaccines offer one method to avoid the drawbacks associated with vaccines derived from whole organisms. This Perspective highlights the improvements and significant recent progress that has been achieved in developing well-defined synthetic vaccines using a variety of molecular antigens.

    • Lyn H. Jones

  • Article |

    The self-assembly of short amphiphilic α-helicomimetic foldamers bearing proteinaceous side-chains can be controlled by manipulating the side-chain sequence. This enables the foldamers to be programmed to form either discrete helical bundles containing isolated cavities, or pH-responsive water-filled channels with controllable pore diameters.

    • Gavin W. Collie
    • , Karolina Pulka-Ziach
    •  & Gilles Guichard

  • News & Views |

    A pair of artificial DNA bases have now been shown to adopt an edge-to-edge geometry in DNA which is similar that found in Watson–Crick base pairing. Aptamers containing these bases have also been shown to bind more strongly to a target than those developed using only the four naturally occurring bases.

    • Cheulhee Jung
    •  & Andrew D. Ellington

  • Article |

    The rapid and selective regulation of a target protein within living cells containing closely related family members is a longstanding challenge. Now the introduction of genetically directed bioorthogonal ligand tethering (BOLT) and the demonstration of selective inhibition (iBOLT) and optical switching (photo-BOLT) of protein function in live mammalian cells addresses this challenge.

    • Yu-Hsuan Tsai
    • , Sebastian Essig
    •  & Jason W. Chin

  • News & Views |

    Analysing post-translational modifications of histone proteins as they occur within chromatin is challenging due to their large number and chemical diversity. A major step forward has now been achieved by using split intein chemistry to engineer functionalized histones within cells.

    • Wolfgang Fischle
    • , Dirk Schwarzer
    •  & Henning D. Mootz

  • News & Views |

    Live-attenuated viruses used in vaccines can regain their virulence, which for deadly viruses such as HIV is an unacceptable risk. Now, attenuated HIV-1 viruses, which include mutations that genetically encode unnatural amino acids and prevent them from replicating in normal cells, have been constructed.

    • Shixian Lin
    •  & Peng R. Chen

  • News & Views |

    Labelling of proteins with pairs of fluorophores enables their conformations to be studied; however, complete incorporation of labels in multiple, pre-defined locations is very difficult. Now, a combination of double unnatural amino acid mutagenesis and selective chemical modification offers a general method to achieve this.

    • E. James Petersson
    •  & John B. Warner

  • Article |

    A series of quadruplet decoding tRNAs has been developed to form an optimized orthogonal translation system. These tRNAs enable efficient, site-specific incorporation of multiple unnatural amino acids into a protein, with a substantial increase in yield over previous methods. The amino acids are then used to site-specifically label a protein with a pair of fluorophores, enabling studies of the protein's dynamics.

    • Kaihang Wang
    • , Amit Sachdeva
    •  & Jason W. Chin

  • Article |

    Compartmentalization of complex chemical networks is an essential step towards the creation of cell-scale molecular systems. The encapsulation of a synthetic biochemical oscillating reaction system into cell-sized emulsion droplets is now demonstrated; a large variability in its oscillatory dynamics is observed, which is attributed to partitioning effects.

    • Maximilian Weitz
    • , Jongmin Kim
    •  & Friedrich C. Simmel

  • News & Views |

    An RNA replicase ribozyme has long been sought by chemists interested in the origin of life. Now, a selection strategy employing a low-temperature water–ice mixture as the medium has led to discovery of a ribozyme that can catalyse polymerization of an RNA chain greater than its own length.

    • Niles Lehman

  • Article |

    Molecular self-replication through ribozyme-catalysed RNA synthesis could shed light on the origins of life. Here, a polymerase ribozyme capable of synthesizing an RNA sequence longer than itself is described, based on a cold-adapted ribozyme variant evolved in ice. This process demonstrates the potential for the emergence of novel ribozyme phenotypes in altered reaction environments.

    • James Attwater
    • , Aniela Wochner
    •  & Philipp Holliger

  • Article |

    Selective carbohydrate binding is a difficult task, usually accomplished by proteins (lectins) or complex synthetic analogues. It has now been achieved by a remarkably simple compound, accessible in just five steps from commercially available materials. This new receptor is highly selective for all-equatorial carbohydrates, and may be used to sense glucose through changes in anthracene fluorescence.

    • Chenfeng Ke
    • , Harry Destecroix
    •  & Anthony P. Davis

  • Article |

    The design and synthesis of a family of chiral and conformationally constrained oligomers is described. Asymmetric synthesis of the monomers is presented and the preparation of a 160,000-member library of diverse tetramers via split-and-pool methods is discussed. From this library, a non-covalent ligand to the DNA-binding domain of p53 was discovered.

    • Claudio Aquino
    • , Mohosin Sarkar
    •  & Glenn C. Micalizio

  • News & Views |

    The self-reproduction of a giant lipid vesicle has been linked to the replication of encapsulated DNA — a promising combination for the construction of a minimalistic synthetic cell.

    • Pier Luigi Luisi
    •  & Pasquale Stano

  • Article |

    Whereas synthetic DNA nanostructures are widely studied, the use of RNA as a structural building block is much less common. Now, it has been shown that tRNA molecules can be designed to assemble into a rigid and thermally stable square antiprism structure that may prove useful for delivery applications inside cells.

    • Isil Severcan
    • , Cody Geary
    •  & Luc Jaeger

Browse broader subjects

Browse Synthetic biology across other nature.com journals