Biosynthesis articles within Nature

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  • Article
    | Open Access

    QS-21—an FDA-approved vaccine adjuvant—and several structural analogues of QS-21 can be synthesized in engineered yeast strains, and this process is much less laborious compared with the conventional mode of extraction from the Chilean soapbark tree.

    • Yuzhong Liu
    • , Xixi Zhao
    •  & Jay D. Keasling

  • Article |

    Computers equipped with a comprehensive knowledge-base of mechanistic steps augmented by physical-organic chemistry rules, as well as quantum mechanical and kinetic calculations, can use a reaction-network approach to analyse the mechanisms of cationic rearrangements.

    • Tomasz Klucznik
    • , Leonidas-Dimitrios Syntrivanis
    •  & Bartosz A. Grzybowski

  • Article |

    Leveraging enzymatic selectivity, a single reaction stream provides a single diastereomer of the cyclic dinucleotide MK-1454, a promising immune-oncology drug candidate, without the use of protecting groups or chiral auxiliaries.

    • John A. McIntosh
    • , Zhijian Liu
    •  & Matthew L. Maddess

  • Article
    | Open Access

    Structural and spectroscopic studies show how a B12-dependent radical SAM enzyme catalyses unique and challenging alkylation chemistry, including protein post-translational modification required for methane biosynthesis.

    • Cameron D. Fyfe
    • , Noelia Bernardo-García
    •  & Olivier Berteau

  • Article |

    The discovery and synthesis of a colistin congener provide a promising clinical lead against mcr-1-encoding colistin-resistant pathogens, which are responsible for an increasing number of deaths from antibiotic-resistant infections.

    • Zongqiang Wang
    • , Bimal Koirala
    •  & Sean F. Brady

  • Article |

    Analysis of two homologous groups of fungal pericyclases demonstrates how they can catalyse either an Alder-ene reaction—which has not previously been found in nature—or a hetero-Diels–Alder reaction.

    • Masao Ohashi
    • , Cooper S. Jamieson
    •  & Yi Tang

  • Letter |

    Microbial generation of a terminal-alkyne-containing amino acid can be encoded into E. coli and provides the potential for in vivo generation of proteins and natural products for click chemistry.

    • J. A. Marchand
    • , M. E. Neugebauer
    •  & M. C. Y. Chang

  • Letter |

    A genetically encoded platform can produce chiral organoboranes in bacteria with high turnover, enantioselectivity and chemoselectivity, and can be tuned and configured through DNA manipulation.

    • S. B. Jennifer Kan
    • , Xiongyi Huang
    •  & Frances H. Arnold

  • Letter |

    WebX-ray crystal structures are presented of each major step of the assembly-line synthesis by the initiation module of the nonribosomal peptide synthetase (NRPS) LgrA; the structures reveal large conformational changes, demonstrating a requirement for NRPSs to be very dynamic.

    • Janice M. Reimer
    • , Martin N. Aloise
    •  & T. Martin Schmeing

  • Letter |

    Glycopeptide antibiotics are biosynthesized by non-ribosomal peptide synthetases, which contain a previously uncharacterized ‘X-domain’ now shown to recruit three cytochrome P450 oxygenases that are necessary for the antibiotics to achieve their final, active conformation.

    • Kristina Haslinger
    • , Madeleine Peschke
    •  & Max J. Cryle

  • Letter |

    A highly specific chemical crosslinking method is used to trap a complex between an acyl carrier protein and a fatty acid dehydratase during fatty acid biosynthesis; subsequent X-ray crystallography, NMR spectroscopy and molecular dynamics simulations techniques enable the detailed study of this complex.

    • Chi Nguyen
    • , Robert W. Haushalter
    •  & Michael D. Burkart

  • Letter |

    This study shows the structural and biochemical characterization of a new type of polyketide synthase module that catalyses the vinylogous addition of a malonyl unit to an unsaturated thioester, generating a branch in the growing polyketide chain; this characterization provides a mechanism by which the structural diversity of polyketide natural products can be increased.

    • Tom Bretschneider
    • , Joel B. Heim
    •  & Christian Hertweck

  • Letter |

    Here, the authors identify a previously unknown regulatory strategy used by Escherichia coli to control end-product levels of the pyrimidine biosynthetic pathway: this involves feedback regulation of the near-terminal pathway enzyme UMP kinase, with accumulation of UMP prevented by its degradation to uridine through UmpH, a phosphatase with a previously unknown function.

    • Marshall Louis Reaves
    • , Brian D. Young
    •  & Joshua D. Rabinowitz

  • News & Views Forum |

    Synthetic chemistry has long been used to prepare useful compounds — especially those that are hard to obtain from natural sources. But synthetic biology is coming of age as an alternative strategy. A biologist and two chemists debate the merits of their fields' synthetic prowess.

    • Jay D. Keasling
    • , Abraham Mendoza
    •  & Phil S. Baran

  • News & Views |

    Eyewitnesses are sometimes asked to identify a culprit from a line-up of people associated with a crime scene. An enzyme — iridoid synthase — that catalyses an unusual reaction has been identified by a similar approach. See Letter p.138

    • Joe Chappell

  • Letter |

    Iridoids are a large family of bicyclic natural products that possess anticancer, anti-inflammatory, antifungal and antibacterial activities; here the essential cyclization step in their biosynthesis is identified, opening up the possibility of production of naturally occurring and synthetic variants of iridoids for use in pharmacy or agriculture.

    • Fernando Geu-Flores
    • , Nathaniel H. Sherden
    •  & Sarah E. O’Connor

  • Letter |

    Atpif1, a mitochondrial ATPase inhibitor, was identified as a zebrafish anemic mutant, pinotage, providing an important link in our understanding of the relationship between mitochondrial homeostasis and haem synthesis and identifying a gene that may have a role in human iron, haem and mitochondrial diseases.

    • Dhvanit I. Shah
    • , Naoko Takahashi-Makise
    •  & Barry H. Paw

  • Letter |

    The M2 isoform of pyruvate kinase (PKM2) is a key glycolytic enzyme that is overexpressed in cancer cells; here, serine is shown to bind to and directly activate PKM2, and the resulting reduction in enzyme activity under serine-deprivation conditions is shown to lead to the diversion of glucose-derived carbon to promote serine biosynthesis required for cell proliferation.

    • Barbara Chaneton
    • , Petra Hillmann
    •  & Eyal Gottlieb

  • Article |

    Atomic-resolution time courses of phosphodiester bond formation catalysed by DNA polymerase η reveal transient intermediate states and an unexpected third metal ion in the reaction mechanism.

    • Teruya Nakamura
    • , Ye Zhao
    •  & Wei Yang

  • News & Views |

    The naturally occurring antibiotic lasalocid A contains a chemical structure that is not expected to form readily. The enzyme that catalyses the formation of this structure has been identified, and its activity is a revelation. See Letter p.355

    • David E. Cane

  • News & Views |

    The biosynthetic route to a naturally occurring insecticide, spinosyn A, has been established. One of the enzymes involved might catalyse a reaction that, although widely used by chemists, has proved elusive in nature. See Letter p.109

    • Wendy L. Kelly

  • Letter |

    Pyrrolysine is the twenty-second naturally occurring amino acid, and it is required for the formation of methane from methylamines. Pyrrolysine is the last remaining natural amino acid with a poorly characterized biosynthetic pathway. Here it is shown that the radical SAM protein PylB converts lysine to 3-methylornithine, which then undergoes a PylC-catalysed condensation with another lysine to generate a product that is oxidized by PylD to generate pyrrolysine.

    • Marsha A. Gaston
    • , Liwen Zhang
    •  & Joseph A. Krzycki

  • Letter |

    The first X-ray crystal structure of a diterpene cyclase is reported — this enzyme, taxadiene synthase, catalyses the cyclization of an isoprenoid in the first committed step of the biosynthesis of the cancer chemotherapeutic drug Taxol. The C-terminal catalytic domain binds and activates the substrate in a manner seen in class I terpenoid cyclases, but the N-terminal domain and a third 'insertion' domain together adopt the fold of a class II terpenoid cyclase. It is proposed that this enzyme could be the ancestral progenitor of all terpenoid cyclases.

    • Mustafa Köksal
    • , Yinghua Jin
    •  & David W. Christianson

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