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
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 formsî—¸MXene nanotubesî—¸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
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
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
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
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