GPAHex-A synthetic biology platform for Type IV–V glycopeptide antibiotic production and discovery

Abstract Glycopeptide antibiotics (GPAs) are essential for the treatment of severe infectious diseases caused by Gram-positive bacteria. The emergence and spread of GPA resistance have propelled the search for more effective GPAs. Given their structural complexity, genetic intractability, and low titer, expansion of GPA chemical diversity using synthetic or medicinal chemistry remains challenging. Here we describe a synthetic biology platform, GPAHex (GPA Heterologous expression), which exploits the genes required for the specialized GPA building blocks, regulation, antibiotic transport, and resistance for the heterologous production of GPAs. Application of the GPAHex platform results in: (1) a 19-fold increase of corbomycin titer compared to the parental strain, (2) the discovery of a teicoplanin-class GPA from an Amycolatopsis isolate, and (3) the overproduction and characterization of a cryptic nonapeptide GPA. GPAHex provides a platform for GPA production and mining of uncharacterized GPAs and provides a blueprint for chassis design for other natural product classes.

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Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production

10.26434/chemrxiv.7765241 ◽

2019 ◽

Author(s):

Sean Lund ◽

Taylor Courtney ◽

Gavin Williams

Keyword(s):

Synthetic Biology ◽

Building Blocks ◽

Isoprenoid Biosynthesis ◽

Thermoplasma Acidophilum ◽

Substrate Promiscuity ◽

Enzymatic Pathways ◽

First Time ◽

Rate Limiting ◽

Alcohol Dependent ◽

Isopentenyl Phosphate

Isoprenoids are a large class of natural products with wide-ranging applications. Synthetic biology approaches to the manufacture of isoprenoids and their new-to-nature derivatives are limited due to the provision in Nature of just two hemiterpene building blocks for isoprenoid biosynthesis. To address this limitation, artificial chemo-enzymatic pathways such as the alcohol-dependent hemiterpene pathway (ADH) serve to leverage consecutive kinases to convert exogenous alcohols to pyrophosphates that could be coupled to downstream isoprenoid biosynthesis. To be successful, each kinase in this pathway should be permissive of a broad range of substrates. For the first time, we have probed the promiscuity of the second enzyme in the ADH pathway, isopentenyl phosphate kinase from Thermoplasma acidophilum, towards a broad range of acceptor monophosphates. Subsequently, we evaluate the suitability of this enzyme to provide non-natural pyrophosphates and provide a critical first step in characterizing the rate limiting steps in the artificial ADH pathway.<br>

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2D-3D integration of hexagonal boron nitride and a high-κ dielectric for ultrafast graphene-based electro-absorption modulators

Nature Communications ◽

10.1038/s41467-021-20926-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hitesh Agarwal ◽

Bernat Terrés ◽

Lorenzo Orsini ◽

Alberto Montanaro ◽

Vito Sorianello ◽

...

Keyword(s):

Boron Nitride ◽

Hafnium Oxide ◽

High Speed ◽

Hexagonal Boron Nitride ◽

Temperature Stability ◽

Cost Effective ◽

Fold Increase ◽

Building Blocks ◽

High Quality ◽

New Device

AbstractElectro-absorption (EA) waveguide-coupled modulators are essential building blocks for on-chip optical communications. Compared to state-of-the-art silicon (Si) devices, graphene-based EA modulators promise smaller footprints, larger temperature stability, cost-effective integration and high speeds. However, combining high speed and large modulation efficiencies in a single graphene-based device has remained elusive so far. In this work, we overcome this fundamental trade-off by demonstrating the 2D-3D dielectric integration in a high-quality encapsulated graphene device. We integrated hafnium oxide (HfO2) and two-dimensional hexagonal boron nitride (hBN) within the insulating section of a double-layer (DL) graphene EA modulator. This combination of materials allows for a high-quality modulator device with high performances: a ~39 GHz bandwidth (BW) with a three-fold increase in modulation efficiency compared to previously reported high-speed modulators. This 2D-3D dielectric integration paves the way to a plethora of electronic and opto-electronic devices with enhanced performance and stability, while expanding the freedom for new device designs.

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Intergrowth of niobium tungsten oxides of the tetragonal tungsten bronze type

Zeitschrift für Naturforschung B ◽

10.1515/znb-2020-0107 ◽

2020 ◽

Vol 75 (11) ◽

pp. 913-919

Author(s):

Frank Krumeich

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Tungsten Bronze ◽

Structural Complexity ◽

Dark Field ◽

Tetragonal Tungsten Bronze ◽

Tungsten Oxides ◽

Transmission Electron ◽

Scanning Transmission

AbstractSince the 1970s, high-resolution transmission electron microscopy (HRTEM) is well established as the most appropriate method to explore the structural complexity of niobium tungsten oxides. Today, scanning transmission electron microscopy (STEM) represents an important alternative for performing the structural characterization of such oxides. STEM images recorded with a high-angle annular dark field (HAADF) detector provide not only information about the cation positions but also about the distribution of niobium and tungsten as the intensity is directly correlated to the local scattering potential. The applicability of this method is demonstrated here for the characterization of the real structure of Nb7W10O47.5. This sample contains well-ordered domains of Nb8W9O47 and Nb4W7O31 besides little ordered areas according to HRTEM results. Structural models for Nb4W7O31 and twinning occurring in this phase have been derived from the interpretation of HAADF-STEM images. A remarkable grain boundary between well-ordered domains of Nb4W7O31 and Nb8W9O47 has been found that contains one-dimensionally periodic features. Furthermore, short-range order observed in less ordered areas could be attributed to an intimate intergrowth of small sections of different tetragonal tungsten bronze (TTB) based structures.

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