5 research outputs found

    Ti<sub>2</sub>CO<sub>2</sub> Nanotubes with Negative Strain Energies and Tunable Band Gaps Predicted from First-Principles Calculations

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    MXenes, a series of two-dimensional (2D) layered early transition metal carbide, nitride, and carbonitride, have been prepared by exfoliating MAX phases recently. In addition to 2D planar MXene, one-dimensional tubular formsMXene nanotubesare also expected to form. Herein, we design atomic models for Ti<sub>2</sub>C as well as Ti<sub>2</sub>CO<sub>2</sub> nanotubes in the 1–4 nm diameter range and investigate their basic properties through density functional theory (DFT). It is shown that though the strain energy of Ti<sub>2</sub>C nanotubes are always positive, Ti<sub>2</sub>CO<sub>2</sub> nanotubes have negative strain energies when diameter beyond 2.5 nm, indicating that they could possibly folded from 2D Ti<sub>2</sub>CO<sub>2</sub> nanosheets. Moreover, the band gap of Ti<sub>2</sub>CO<sub>2</sub> nanotubes decrease with the growing diameter and the maximum band gap can reach up to 1.1 eV, over 3 times that of their planar form. Thus, tunable band gaps provide strong evidence for the effectiveness of nanostructuring on the electronic properties of Ti<sub>2</sub>CO<sub>2</sub> nanotubes

    Essential Role of the Donor Acyl Carrier Protein in Stereoselective Chain Translocation to a Fully Reducing Module of the Nanchangmycin Polyketide Synthase

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    Incubation of recombinant module 2 of the polyether nanchangmycin synthase (NANS), carrying an appended thioesterase domain, with the ACP-bound substrate (2<i>RS</i>)-2-methyl-3-ketobutyryl-NANS_ACP1 (<b>2-ACP1</b>) and methylmalonyl-CoA in the presence of NADPH gave diastereomerically pure (2<i>S</i>,4<i>R</i>)-2,4-dimethyl-5-ketohexanoic acid (<b>4a</b>). These results contrast with the previously reported weak discrimination by NANS module 2+TE between the enantiomers of the corresponding <i>N</i>-acetylcysteamine-conjugated substrate analogue (±)-2-methyl-3-ketobutyryl-SNAC (<b>2-SNAC</b>), which resulted in formation of a 5:3 mixture of <b>4a</b> and its (2<i>S</i>,4<i>S</i>)-diastereomer <b>4b</b>. Incubation of NANS module 2+TE with <b>2-ACP1</b> in the absence of NADPH gave unreduced 3,5,6-trimethyl-4-hydroxypyrone (<b>3</b>) with a <i>k</i><sub>cat</sub> of 4.4 ± 0.9 min<sup>–1</sup> and a <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> of 67 min<sup>–1</sup> mM<sup>–1</sup>, corresponding to a ∼2300-fold increase compared to the <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> for the diffusive substrate <b>2-SNAC</b>. Covalent tethering of the 2-methyl-3-ketobutyryl thioester substrate to the NANS ACP1 domain derived from the natural upstream PKS module of the nanchangmycin synthase significantly enhanced both the stereospecificity and the kinetic efficiency of the sequential polyketide chain translocation and condensation reactions catalyzed by the ketosynthase domain of NANS module 2

    Specificity of the Ester Bond Forming Condensation Enzyme SgcC5 in C-1027 Biosynthesis

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    The SgcC5 condensation enzyme catalyzes the attachment of SgcC2-tethered (<i>S</i>)-3-chloro-5-hydroxy-β-tyrosine (<b>2</b>) to the enediyne core in C-1027 (<b>1</b>) biosynthesis. It is reported that SgcC5 (i) exhibits high stereospecificity toward the (<i>S</i>)-enantiomers of SgcC2-tethered β-tyrosine and analogues as donors, (ii) prefers the (<i>R</i>)-enantiomers of 1-phenyl-1,2-ethanediol (<b>3</b>) and analogues, mimicking the enediyne core, as acceptors, and (iii) can recognize a variety of donor and acceptor substrates to catalyze their regio- and stereospecific ester bond formations

    Enediyne Polyketide Synthases Stereoselectively Reduce the β‑Ketoacyl Intermediates to β‑d‑Hydroxyacyl Intermediates in Enediyne Core Biosynthesis

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    PKSE biosynthesizes an enediyne core precursor from decarboxylative condensation of eight malonyl-CoAs. The KR domain of PKSE is responsible for iterative β-ketoreduction in each round of polyketide chain elongation. KRs from selected PKSEs were investigated in vitro with β-ketoacyl-SNACs as substrate mimics. Each of the KRs reduced the β-ketoacyl-SNACs stereoselectively, all affording the corresponding β-d-hydroxyacyl-SNACs, and the catalytic efficiencies (<i>k</i><sub>cat</sub>/<i>K</i><sub>M</sub>) of the KRs increased significantly as the chain length of the β-ketoacyl-SNAC substrate increases

    PokMT1 from the Polyketomycin Biosynthetic Machinery of <i>Streptomyces diastatochromogenes</i> Tü6028 Belongs to the Emerging Family of <i>C</i>‑Methyltransferases That Act on CoA-Activated Aromatic Substrates

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    Recent biochemical characterizations of the MdpB2 CoA ligase and MdpB1 <i>C</i>-methyltransferase (<i>C</i>-MT) from the maduropeptin (MDP, <b>2</b>) biosynthetic machinery revealed unusual pathway logic involving C-methylation occurring on a CoA-activated aromatic substrate. Here we confirmed this pathway logic for the biosynthesis of polyketomycin (POK, <b>3</b>). Biochemical characterization unambiguously established that PokM3 and PokMT1 catalyze the sequential conversion of 6-methylsalicylic acid (6-MSA, <b>4</b>) to form 3,6-dimethylsalicylyl-CoA (3,6-DMSA-CoA, <b>6</b>), which serves as the direct precursor for the 3,6-dimethylsalicylic acid (3,6-DMSA) moiety in the biosynthesis of <b>3</b>. PokMT1 catalyzes the C-methylation of 6-methylsalicylyl-CoA (6-MSA-CoA, <b>5</b>) with a <i>k</i><sub>cat</sub> of 1.9 min<sup>–1</sup> and a <i>K</i><sub>m</sub> of 2.2 ± 0.1 μM, representing the most proficient <i>C</i>-MT characterized to date. Bioinformatics analysis of MTs from natural product biosynthetic machineries demonstrated that PokMT1 and MdpB1 belong to a phylogenetic clade of <i>C</i>-MTs that preferably act on aromatic acids. Significantly, this clade includes the structurally characterized enzyme SibL, which catalyzes C-methylation of 3-hydroxykynurenine in its free acid form, using two conserved tyrosine residues for catalysis. A homology model and site-directed mutagenesis suggested that PokMT1 also employs this unusual arrangement of tyrosine residues to coordinate C-methylation but revealed a large cavity capable of accommodating the CoA moiety tethered to <b>5</b>. CoA activation of the aromatic acid substrate may represent a general strategy that could be exploited to improve catalytic efficiency. This study sets the stage to further investigate and exploit the catalytic utility of this emerging family of <i>C</i>-MTs in biocatalysis and synthetic biology
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