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Scientific Reports Jun 2024Microbial NAT enzymes, which employ acyl-CoA to acylate aromatic amines and hydrazines, have been well-studied for their role in xenobiotic metabolism. Some homologues...
Microbial NAT enzymes, which employ acyl-CoA to acylate aromatic amines and hydrazines, have been well-studied for their role in xenobiotic metabolism. Some homologues have also been linked to secondary metabolism, but this function of NAT enzymes is not as well-known. For this comparative study, we surveyed sequenced microbial genomes to update the list of formally annotated NAT genes, adding over 4000 new sequences (mainly bacterial, but also archaeal, fungal and protist) and portraying a broad but not universal distribution of NATs in the microbiocosmos. Localization of NAT sequences within microbial gene clusters was not a rare finding, and this association was evident across all main types of biosynthetic gene clusters (BGCs) implicated in secondary metabolism. Interrogation of the MIBiG database for experimentally characterized clusters with NAT genes further supports that secondary metabolism must be a major function for microbial NAT enzymes and should not be overlooked by researchers in the field. We also show that NAT sequences can be associated with bacterial plasmids potentially involved in horizontal gene transfer. Combined, our computational predictions and MIBiG literature findings reveal the extraordinary functional diversification of microbial NAT genes, prompting further research into their role in predicted BGCs with as yet uncharacterized function.
Topics: Multigene Family; Secondary Metabolism; Bacteria; Archaea; Phylogeny; Arylamine N-Acetyltransferase; Fungi; Genomics; Gene Transfer, Horizontal
PubMed: 38942826
DOI: 10.1038/s41598-024-65342-4 -
Journal of Natural Products Jun 2024The marine tunicate-derived RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based...
The marine tunicate-derived RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based molecular networking analysis enhanced with nonparametric statistics highlighted the upregulation of a molecular cluster (Kruskal-Wallis = 1.6 e for ) in which no MS/MS features had library matches. Targeted isolation of these features resulted in the discovery of nine new acylated lipopeptides, albubactins A-H (-) each containing a unique glutamine tripeptide and a -terminal ethyl ester moiety. Three related albubactin acids A-C (-) lacking the ethyl ester were also identified. NMR spectroscopy and UPLC-HR-ESI-MS/MS demonstrated that the albubactins were obtained as mixtures that shared a common / and differed only in their acylated terminal groups. Due to the complex spectroscopic elucidation with many overlapping shifts, a total synthesis of albubactin A () was completed and used to determine the absolute configuration of the new albubactins.
PubMed: 38940698
DOI: 10.1021/acs.jnatprod.3c01234 -
ACS Applied Materials & Interfaces Jun 2024Harvesting solar energy to produce value-added chemicals from carbon dioxide (CO) presents a promising route for addressing the complexities of sustainable energy... (Review)
Review
Harvesting solar energy to produce value-added chemicals from carbon dioxide (CO) presents a promising route for addressing the complexities of sustainable energy systems and environmental issues. In this context, the development of metal-coordinated porous organic polymers (POPs) offers a vital avenue for improving the photocatalytic performance of organic motifs. The current study presents a metal-integrated photocatalytic system (namely, ) developed via a one-pot Friedel-Crafts (F.C.) acylation strategy, for solid-gas phase photochemical CO reduction to CO (CORR). The postsynthetic incorporation of metal (Zn) active sites on the host polymeric backbone of significantly influences the catalytic activity. Notably, demonstrates good photocatalytic performance in the absence of any cocatalyst and photosensitizer yielding CO while impeding the competitive hydrogen evolution reaction (HER) from water. The experimental findings collectively propose that the observed catalytic activity and selectivity arise from the synergistic interplay between the singular zinc catalytic centers and the light-harvesting capacity of the highly conjugated polymeric backbone. Further, X-ray absorption spectroscopy (XAS) analysis has significantly highlighted the prominent role played by the ZnNO single sites in the polymeric framework for activating the gaseous CO molecules. Further, time-dependent density functional theory (DFT) analysis also reveals the thermodynamic feasibility of CORR over HER under optimized reaction conditions. This work cumulatively presents an effective strategy to demonstrate the importance of metal-active sites and effectively establish their structure-activity relationship during photocatalysis.
PubMed: 38940318
DOI: 10.1021/acsami.4c06198 -
JACS Au Jun 2024The first total synthesis of the repeating units of the -antigens of ATCC 27577, O10, and O19 was achieved via a linear glycosylation strategy. This also represents the...
The first total synthesis of the repeating units of the -antigens of ATCC 27577, O10, and O19 was achieved via a linear glycosylation strategy. This also represents the first synthesis of an oligosaccharide containing an α-linked -acetyl-l-galactosaminuronic acid (l-GalNAcA) unit. All of the glycosyl linkages, including three challenging 1,2--glycosidic bonds of amino sugars, were effectively constructed with high to exclusive stereoselectivity, while orthogonal protection tactics were employed to facilitate regioselective glycosylations and the introduction of a variety of functionalities. An acetyl group migration phenomenon was found during the synthesis of the -acylated repeating unit of the ATCC 27577 antigen. All synthetic targets carried an amino functional group in the linker at the reducing end, thus facilitating further regioselective elaboration and biological studies. The synthetic strategy established here should be useful for the preparation of other similar oligosaccharides.
PubMed: 38938791
DOI: 10.1021/jacsau.4c00321 -
Advances in Pharmacological and... 2024Gonococcal infections present a notable public health issue, and the major approach for treatment involves using -lactam antibiotics that specifically target...
Investigation into the Interaction between Penicillin-Resistant and Penicillin-Susceptible Gonococcal Penicillin-Binding Protein 2 and Target Phenolic Ligands through Molecular Docking Studies and Structure-Activity Relationship Analysis.
Gonococcal infections present a notable public health issue, and the major approach for treatment involves using -lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in . This study examines the influence of flavonoids, namely, rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research starts by clarifying the structural effects of certain mutations, such as the insertion of an aspartate residue at position 345 (Asp-345a), in the PBP2. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely, P551S and F504L, have a significant impact on the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasising rutin's exceptional binding affinity and its potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments, namely, in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in . Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant bacteria. The verified simulation outcomes establish a basis for the creation of potent inhibitors and medicinal therapies to combat infectious illnesses.
PubMed: 38938595
DOI: 10.1155/2024/2585922 -
Angewandte Chemie (International Ed. in... Jun 2024Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more...
Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late-stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non-native moieties. Utilising an allenamide, we report the first semi-synthesis of antimicrobial lipopeptides leveraging a highly efficient thia-Michael addition of chemically diverse lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as a model scaffold, an optimised allenamide-mediated thia-Michael addition effected rapid and near quantitative lipidation, affording vinyl sulfide-linked lipopeptide derivatives. Harnessing the utility of this new methodology, 22 lipophilic thiols of unprecedented chemical diversity were introduced to the PMBN framework. These included alkyl thiols, substituted aromatic thiols, heterocyclic thiols and those bearing additional functional groups (e.g., amines), ultimately yielding analogues with potent Gram-negative antimicrobial activity and substantially attenuated nephrotoxicity. Furthermore, we report facile routes to transform the allenamide into a β-keto amide on unprotected peptides, offering a powerful "jack-of-all-trades" synthetic intermediate to enable further peptide modification.
PubMed: 38932510
DOI: 10.1002/anie.202407764 -
Plants (Basel, Switzerland) Jun 2024An investigation of phenolic glycosides extracted from germplasm revealed that arbusculoidin (benzyl 1--β-d-glucopyranosyl-1-hydroxy-6-oxo-2-cyclohexenyl carboxylate)...
An investigation of phenolic glycosides extracted from germplasm revealed that arbusculoidin (benzyl 1--β-d-glucopyranosyl-1-hydroxy-6-oxo-2-cyclohexenyl carboxylate) and its enolic 6-glycoside isomer, isoarbusculoidin, are widespread across the Salix family. An analysis of natural hybrid species and progeny from a willow breeding programme demonstrated that the putative biosynthetic pathway leading to the salicinoid family of phenolic glycosides runs in parallel to a "benzyl"-based pathway to arbusculoidin. The introduction of a known Diels-Alder reaction trait from , as well as an acylation trait, into progeny containing both salicyl- and benzyl- pathways caused the formation of all possible hetero-cyclodimers from mixtures of reactive dienone (acyl)glycosides that participated in cross-over reactions. In addition to providing access to new analogues of the anti-cancer dimer miyabeacin, the analysis of the breeding progeny also indicated that these dienone (acyl)glycosides are stable in planta. Although the immediate biosynthetic precursors of these compounds remain to be defined, the results suggest that the (acyl)glycosylation reactions may occur later in the pathway than previously suggested by in vitro work on cloned UGT enzymes.
PubMed: 38931042
DOI: 10.3390/plants13121609 -
Molecules (Basel, Switzerland) Jun 2024A new series of chiral 4,5-dihydro-1-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition...
Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.
A new series of chiral 4,5-dihydro-1-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (-) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the ()-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.
Topics: Humans; Crystallography, X-Ray; Triazoles; Cell Line, Tumor; Antineoplastic Agents; Carbohydrates; Molecular Structure; Stereoisomerism; Acetylation; Structure-Activity Relationship; Magnetic Resonance Spectroscopy
PubMed: 38930904
DOI: 10.3390/molecules29122839 -
Medicina (Kaunas, Lithuania) May 2024Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial... (Review)
Review
Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial pathological feature of CKD and ESRD. However, there is no effective treatment for this condition. Despite the complex molecular mechanisms involved in renal fibrosis, increasing evidence highlights the crucial role of histone modification in its regulation. The reversibility of histone modifications offers promising avenues for therapeutic strategies to block or reverse renal fibrosis. Therefore, a comprehensive understanding of the regulatory implications of histone modifications in fibrosis may provide novel insights into more effective and safer therapeutic approaches. This review highlights the regulatory mechanisms and recent advances in histone modifications in renal fibrosis, particularly histone methylation and histone acetylation. The aim is to explore the potential of histone modifications as targets for treating renal fibrosis.
Topics: Humans; Fibrosis; Histones; Renal Insufficiency, Chronic; Kidney; Acetylation; Methylation; Protein Processing, Post-Translational; Histone Code
PubMed: 38929505
DOI: 10.3390/medicina60060888 -
Foods (Basel, Switzerland) Jun 2024The wide ampelographic treasure of Italian wine grape varieties is driving research towards suitable approaches for the varietal authenticity control of wine. In this...
The wide ampelographic treasure of Italian wine grape varieties is driving research towards suitable approaches for the varietal authenticity control of wine. In this paper, Aglianico, Negroamaro, Primitivo and Uva di Troia red wines, which were produced experimentally by single-grape winemaking from non-aromatic grapes native to southern Italy, were analyzed with respect to berry markers, namely anthocyanins, hydroxycinnamic acids (HPLC-DAD), shikimic acid (HPLC-UV) and glycosidic aroma precursors (GC-MS). The study confirms that, just as for the berries, useful varietal authenticity markers for red wine, even after aging, turn out to be hydroxycinnamic acids, relative amounts of acylated forms of anthocyanins, and shikimic acid, together with some grape glycosidic precursors from terpenes and C- norisoprenoids. Principal Component Analysis was used as a valuable tool to highlight the results.
PubMed: 38928808
DOI: 10.3390/foods13121866