Flexizyme-Enabled Benchtop Biosynthesis of Thiopeptides

Thiopeptides are natural antibiotics that are fashioned from short peptides by multiple layers of post-translational modification. Their biosynthesis, in particular the pyridine synthases that form the macrocyclic antibiotic core, has attracted intensive research but is complicated by the challenges of reconstituting multiple-pathway enzymes. By combining select RiPP enzymes with cell free expression and flexizyme-based codon reprogramming, we have developed a benchtop biosynthesis of thiopeptide scaffolds. This strategy side-steps several challenges related to the investigation of thiopeptide enzymes and allows access to analytical quantities of new thiopeptide analogs. We further demonstrate that this strategy can be used to validate the activity of new pyridine synthases without the need to reconstitute the cognate prior pathway enzymes

Structure of the icosahedral Ti-Zr-Ni quasicrystal

The atomic structure of the icosahedral Ti-Zr-Ni quasicrystal is determined by invoking similarities to periodic crystalline phases, diffraction data and the results from ab initio calculations. The structure is modeled by decorations of the canonical cell tiling geometry. The initial decoration model is based on the structure of the Frank-Kasper phase W-TiZrNi, the 1/1 approximant structure of the quasicrystal. The decoration model is optimized using a new method of structural analysis combining a least-squares refinement of diffraction data with results from ab initio calculations. The resulting structural model of icosahedral Ti-Zr-Ni is interpreted as a simple decoration rule and structural details are discussed.Comment: 12 pages, 8 figure

Quantum Griffiths effects and smeared phase transitions in metals: theory and experiment

In this paper, we review theoretical and experimental research on rare region effects at quantum phase transitions in disordered itinerant electron systems. After summarizing a few basic concepts about phase transitions in the presence of quenched randomness, we introduce the idea of rare regions and discuss their importance. We then analyze in detail the different phenomena that can arise at magnetic quantum phase transitions in disordered metals, including quantum Griffiths singularities, smeared phase transitions, and cluster-glass formation. For each scenario, we discuss the resulting phase diagram and summarize the behavior of various observables. We then review several recent experiments that provide examples of these rare region phenomena. We conclude by discussing limitations of current approaches and open questions.Comment: 31 pages, 7 eps figures included, v2: discussion of the dissipative Ising chain fixed, references added, v3: final version as publishe

An On/Off Lattice Approach to Protein Structure Prediction from Contact Maps

Abstract. An important unsolved problem in structural bioinformatics is that of protein structure prediction (PSP), the reconstruction of a biologically plausible three-dimensional structure for a given protein given only its amino acid sequence. The PSP problem is of enormous interest, because the function of proteins is a direct consequence of their three-dimensional structure. Approaches to solve the PSP use protein models that range from very realistic (all-atom) to very simple (on a lattice). Finer representations usually generate better candidate structures, but are computationally more costly than the simpler on-lattice ones. In this work we propose a combined approach that makes use of a simple and fast lattice protein structure prediction algorithm, REMC-HPPFP, to compute a number of coarse candidate structures. These are later refined by 3Distill, an off-lattice, residue-level protein structure predictor. We prove that the lattice algorithm is able to bootstrap 3Distill, which consequently converges much faster, allowing for shorter execution times without noticeably degrading the quality of the predictions. This novel method allows us to generate a large set of decoys of quality comparable to those computed by the off-lattice method alone, but using a fraction of the computations. As a result, our method could be used to build large databases of predicted decoys for analysis, or for selecting the best candidate structures through reranking techniques. Furthermore our method is generic, in that it can be applied to other algorithms than 3Distill