A5020048735- Biochemical and Molecular Research
- Enzyme Structure and Function
- Metalloenzymes and iron-sulfur proteins
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Carbohydrate Chemistry and Synthesis
- CO2 Reduction Techniques and Catalysts
- Marine Sponges and Natural Products
- Enzyme Production and Characterization
- Vitamin K Research Studies
- Metal-Catalyzed Oxygenation Mechanisms
- Infection Control and Ventilation
- Bioactive Compounds and Antitumor Agents
- Glycosylation and Glycoproteins Research
- Biochemical Acid Research Studies
- Methane Hydrates and Related Phenomena
- Listeria monocytogenes in Food Safety
- Biofuel production and bioconversion
- Essential Oils and Antimicrobial Activity
- Plant biochemistry and biosynthesis
- Metabolomics and Mass Spectrometry Studies
- Peptidase Inhibition and Analysis
- Anaerobic Digestion and Biogas Production
- Genomics and Phylogenetic Studies
- Traditional and Medicinal Uses of Annonaceae
Indian Institute of Technology Dharwad
2019-2024
Indian Institute of Technology Guwahati
2019-2024
University of Illinois Urbana-Champaign
2016-2022
Texas A&M University
2012-2019
Indian Institute of Technology Delhi
2007
Methyl-coenzyme M reductase (MCR), found in strictly anaerobic methanogenic and methanotrophic archaea, catalyzes the reversible production consumption of potent greenhouse gas methane. The α subunit MCR (McrA) contains several unusual post-translational modifications, including a rare thioamidation glycine. Based on presumed function homologous genes involved biosynthesis thioviridamide, thioamide-containing natural product, we hypothesized that archaeal tfuA ycaO would be responsible for...
Menaquinone (MK, vitamin K2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential for activation of various proteins involved blood clotting and bone metabolism. Recently, new pathway biosynthesis this cofactor was discovered Streptomyces coelicolor A3(2) which chorismate converted to aminofutalosine reaction catalyzed by MqnA unidentified enzyme. Here, we reconstitute demonstrate missing enzyme...
The biosynthesis of the thiopeptide thiomuracin is a well-orchestrated process involving multitude posttranslational modifications. We show that six Cys residues precursor peptide are first cyclodehydrated and oxidized to thiazoles in an ordered, but nonlinear fashion leader-peptide-dependent. Then four alcohols glutamylated converted alkenes C-to-N terminal directional leader-peptide-independent. Finally, two these undergo formal [4 + 2] cycloaddition form trithiazole-substituted pyridine...
Significance Thioamidation as a posttranslational modification is exceptionally rare, with only one protein example known (methyl-coenzyme M reductase, MCR), well few ribosomal natural products. The genes involved in MCR thioamidation have recently been elucidated, but the enzymes yet to be characterized. Herein, we report vitro reconstitution and substrate preferences of peptidic using peptides derived from methanogenic archaea. We demonstrate that requires an ATP-dependent YcaO enzyme...
YcaO enzymes are known to catalyze the ATP-dependent formation of azoline heterocycles, thioamides, and (macro)lactamidines on peptide substrates. These found in multiple biosynthetic pathways, including those for several different classes ribosomally synthesized post-translationally modified peptides (RiPPs). However, there major knowledge gaps mechanistic structural underpinnings that govern each YcaO-mediated modifications. Here, we present first structure any enzyme bound its substrate...
Thiomuracin is a thiopeptide antibiotic with potent activity toward Gram-positive drug-resistant bacteria. biosynthesized from precursor peptide, TbtA, by complex array of posttranslational modifications. One several intriguing transformations the C-methylation thiazole, occurring at an unactivated sp2 carbon. Herein, we report in vitro reconstitution TbtI, responsible radical S-adenosyl-methionine (rSAM) C-methyltransferase, which catalyzes formation 5-methylthiazole single site. Our...
The radical non-α-carbon thioether peptides (ranthipeptides) are a newly described class of ribosomally synthesized and post-translationally modified peptide (RiPP). Ranthipeptide biosynthetic gene clusters characterized by Cys-rich precursor S-adenosylmethionine (rSAM)-dependent enzyme that forms linkage between Cys donor an acceptor residue. Unlike the sulfur-to-α-carbon linked (sactipeptides), known ranthipeptides contain thioethers to either β- or γ-carbon (i.e., non-α-carbon) Recently,...
Aminofutalosine synthase (MqnE) is a radical SAM enzyme involved in the menaquinone biosynthetic pathway. In this communication, we propose novel mechanism for reaction involving addition of adenosyl to substrate double bond form captodative followed by rearrangement and decarboxylation an aryl anion which then oxidized [4Fe-4S]+2 cluster. Consistent with proposal, describe trapping using triggered C-Br fragmentation reactions. We also replacing vinylic carboxylic acid amide.
The past decade has seen the discovery of four different classes radical S-adenosylmethionine (rSAM) methyltransferases that methylate unactivated carbon centers. Whereas mechanism class A is well understood, molecular details methylation by B–D are not. In this study, we present detailed mechanistic investigations C rSAM methyltransferase TbtI involved in biosynthesis potent thiopeptide antibiotic thiomuracin. C-methylates a Cys-derived thiazole during posttranslational maturation. Product...
The bottromycins belong to the ribosomally synthesized and posttranslationally modified peptide (RiPP) family of natural products. Bottromycins exhibit unique structural features, including a hallmark macrolactamidine ring thiazole heterocycle for which divergent members YcaO superfamily have been biosynthetically implicated. Here we report in vitro reconstitution two proteins, BmbD BmbE, responsible ATP-dependent cyclodehydration reactions that yield thiazoline-...
Pseudouridine (Ψ), the most abundant modification in RNA, is synthesized situ using Ψ synthase. Recently, a pathway for degradation of was described [Preumont, A., Snoussi, K., Stroobant, V., Collet, J. F., and Van Schaftingen, E. (2008) Biol. Chem. 283, 25238-25246]. In this pathway, first converted to 5'-monophosphate (ΨMP) by kinase then ΨMP degraded glycosidase uracil ribose 5-phosphate. example mechanistically characterized enzyme that cleaves C-C glycosidic bond. Here we report X-ray...
Here, we report the therapeutic potential of a natural quinazoline derivative (2-chloro-6-phenyl-8H-quinazolino[4,3-b]quinazolin-8-one) isolated from marine sponge Hyrtios erectus against human breast cancer. The cytotoxicity compound was investigated on carcinoma cell line (MCF-7). Antiproliferative activity estimated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MTT assay showed significant inhibition MCF-7 cells viability with IC50 value 13.04 ± 1.03 µg/mL...
Biosurfactants are eco-friendly surface-active molecules recommended for enhanced oil recovery techniques. In the present study, a potential lipopeptide (biosurfactant) encoding iturin A gene was synthesized from Bacillus aryabhattai. To improvise yield of specific applications, current research tends toward engineering and expressing recombinant peptides. An sequence codon-optimized, amplified with gene-specific primers, ligated into pET-32A expression vector to achieve high-level protein...
Aminofutalosine synthase (MqnE) catalyzes an important rearrangement reaction in menaquinone biosynthesis by the futalosine pathway. In this Letter, we report identification of previously unreported inhibitors MqnE using a mechanism-guided approach. The best inhibitor shows efficient inhibitory activity against H. pylori (IC50 = 1.8 ± 0.4 μM) and identifies as promising target for antibiotic development.