A <sup>13</sup>C‐NMR and IR study of isocyanides and some of their complexes

Stephany, R. W.; Bie, M. J. A. De; Drenth, W.

doi:10.1002/mrc.1270060112

Cited by 109 publications

(55 citation statements)

References 8 publications

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“…The presence of an isonitrile moiety in INLP 1 was further confirmed by comparison with the reported 13 C-14 N nuclear spin coupling constants and IR spectroscopy absorption (Fig. 2) (20). The absolute configuration of the C3′ and C3′′ (both R) was determined by acid hydrolysis to yield the monomer of 3-amino butyric acid, which was then reacted with Marfey's reagent and compared with the standards (Fig.…”

Section: Resultsmentioning

confidence: 57%

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

Harris

Sato

Herman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

132

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A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase. In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport.biosynthetic enzymes | mycobacteria | metal transport S mall-molecule secondary metabolites are produced by microbes as chemical weapons to combat competing organisms or as communication signals to control complex processes such as virulence, morphological differentiation, biofilm formation, and metal acquisition (1-3). One of the most important classes of secondary metabolites are nonribosomal peptides, which are typically biosynthesized by modular nonribosomal peptide synthetases (NRPSs) in an assembly-line manner (4). Two NRPS-encoding gene clusters (mbt and Rv0096-0101) have been identified from the genome of Mycobacterium tuberculosis, the leading causative agent of tuberculosis that currently infects one-third of the world's population. Although the cluster of mbt has been characterized to biosynthesize mycobactin siderophores that form mycobactin-Fe(III) complexes for iron sequestration (5), the role of Rv0096-0101 remains obscure despite various biological studies that have indicated the production of a virulence factor by this gene cluster (6-14). For example, using transposon-site hybridization, Rv0098 to Rv0101 were predicted to be required for M. tuberculosis survival in a mouse model of infection (10). Consistently, a transposon insertion of Rv0097 attenuated M. tuberculosis growth and survival in mice (7).An in silico homology search has revealed that gene clusters homologous to Rv0096-0101 are conserved in pathogenic mycobacteria, such as M. bovis, M. leprae, M. marinum, M. ulcerans, and M. abscessus (Fig. 1), but absent in nonpathogenic mycobacteria such as M. smegmatis, providing further indication of the virulenceassociated nature of the locus product in mycobacteria. Interestingly, in addition to the genus of Mycobacterium, related operons are found in the phylum of Actinobacteria across genera including Streptomyces, Kutzneria, Nocardia, and Rhodococcus (Fig. 1), suggesting a widespread presence of this cluster. Further bioinformatic analysis has shown that five genes (Rv0097-0101) are conserved across all identified gene cluste...

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Section: Resultsmentioning

confidence: 57%

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

Harris

Sato

Herman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

132

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“…The low frequency peak at 2083 cm −1 , assigned to the in conformation, is comparatively broad, and the out conformation peak at 2139 cm −1 has a shoulder at higher frequency for MbCNC1. The addition of alkyl substituents to the CNR C1 atom decreases the bond strength of the zwitterionic isocyanide group through internal steric and inductive effects (37), as indicated by decreases in ν CN of 10 and 30 cm −1 for free ethyl and t-butyl isocyanides, respectively, from the 2187 cm −1 CNC1 peak for these molecules in water (Fig. 1, left panel; Table 1).…”

Section: Resultsmentioning

confidence: 99%

The Stretching Frequencies of Bound Alkyl Isocyanides Indicate Two Distinct Ligand Orientations within the Distal Pocket of Myoglobin

Blouin

Olson

2010

Biochemistry

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The FTIR spectra for alkyl isocyanides (CNRs) change from a single νCN band centered at ~2175 cm−1 to two peaks at ~2075 and ~2125 cm−1 upon binding to sperm whale myoglobin (Mb). The low and high frequency peaks have been assigned to in and out conformations, respectively. In the in conformation, the ligand is pointing toward the protein interior, and the distal His64(E7) is in a closed position, donates a H-bond to the bound isocyano group, enhances back bonding, and lowers the C-N bond order. In the out conformation, the ligand side chain points toward solvent through a channel opened by outward rotation of His64. Loss of positive polarity near the binding site causes an increase in C-N bond order. Support for this interpretation is three-fold: (1) similar shifts to lower frequency occur for MbCO complexes when H-bond donation from His64(E7) occurs; (2) only one peak at ~2125 cm−1, indicative of an apolar environment, is observed for CNRs bound to H64A or H64L Mb mutants or to chelated protoheme in soap micelles; and (3) the fraction of in conformation based on FTIR spectra correlates strongly with the fraction of geminate recombination after nanosecond laser photolysis. The in alkyl side chain conformation causes the photodissociated ligand to be “stuck” in the distal pocket, promoting internal rebinding, whereas the out conformation inhibits geminate recombination because part of the ligand is already in an open E7 channel, poised for rapid escape.

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“…At the end of the 1980′s, Kroto et al recorded the microwave spectrum of the propargyl derivative,24 but the spectrum of the allenyl derivative has been studied much more recently 25. For both compounds, the data on a few significant IR absorptions have been reported,26 and recently, the photoelectron spectra of all these species have been analyzed 19…”

Section: Introductionmentioning

confidence: 99%

Gas‐Phase Infrared Spectra of Three Compounds of Astrochemical Interest: Vinyl, Allenyl, and Propargyl Isocyanides

et al. 2014

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Isocyanides, isomers of the cyanides detected in the interstellar medium, are also possible components of this medium. The infrared spectra (5000-500 cm(-1) ) of gaseous vinyl isocyanide, allenyl isocyanide, and propargyl isocyanide have been recorded at 0.1 cm(-1) resolution. When prepared on a gram scale to produce a partial pressure of 10 mbar after evaporation in the cell, these three isocyanides, which have previously been reported to be kinetically unstable, do not display any sign of decomposition when recording the spectra. Geometry optimizations and harmonic and anharmonic vibrational frequencies were calculated using the LCCSD(T) method with the cc-pVTZ basis set. Anharmonic frequencies of fundamental, overtone, and combination transitions were calculated using a variational approach implemented in the P Anhar.v2.0 code, to assign the experimental data for each compound. These results improve our knowledge of these under-investigated compounds and pave the way for other physicochemical studies on functionalized isocyanides.

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A ¹³C‐NMR and IR study of isocyanides and some of their complexes

Cited by 109 publications

References 8 publications

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

The Stretching Frequencies of Bound Alkyl Isocyanides Indicate Two Distinct Ligand Orientations within the Distal Pocket of Myoglobin

Gas‐Phase Infrared Spectra of Three Compounds of Astrochemical Interest: Vinyl, Allenyl, and Propargyl Isocyanides

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A 13C‐NMR and IR study of isocyanides and some of their complexes

Cited by 109 publications

References 8 publications

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria

The Stretching Frequencies of Bound Alkyl Isocyanides Indicate Two Distinct Ligand Orientations within the Distal Pocket of Myoglobin

Gas‐Phase Infrared Spectra of Three Compounds of Astrochemical Interest: Vinyl, Allenyl, and Propargyl Isocyanides

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A ¹³C‐NMR and IR study of isocyanides and some of their complexes