Obafluorin
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| Category | Antibiotics |
| Catalog number | BBF-05654 |
| CAS | 92121-68-1 |
| Molecular Weight | 358.30 |
| Molecular Formula | C17H14N2O7 |
| Purity | ≥98% |
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Description
It is a β-lactone antibiotic that is found in Pseudomonas fluorescens and is active against Staphylococcus aureus, Streptococcus faecalis, Klebsiella pneumoniae and Pseudomonas vulgaris.
Specification
| Synonyms | Benzamide, 2,3-dihydroxy-N-[(2R,3S)-2-[(4-nitrophenyl)methyl]-4-oxo-3-oxetanyl]-; 2,3-dihydroxy-N-((2R,3S)-2-(4-nitrobenzyl)-4-oxooxetan-3-yl)benzamide; Benzamide, 2,3-dihydroxy-N-[2-[(4-nitrophenyl)methyl]-4-oxo-3-oxetanyl]-, (2R-cis)-; (+)-Obafluorin; N-[(3S)-2-Oxo-4β-(4-nitrobenzyl)oxetan-3β-yl]-2,3-dihydroxybenzamide |
| Storage | Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years) |
| IUPAC Name | 2,3-dihydroxy-N-[(2R,3S)-2-[(4-nitrophenyl)methyl]-4-oxooxetan-3-yl]benzamide |
| Canonical SMILES | C1=CC(=C(C(=C1)O)O)C(=O)NC2C(OC2=O)CC3=CC=C(C=C3)[N+](=O)[O-] |
| InChI | InChI=1S/C17H14N2O7/c20-12-3-1-2-11(15(12)21)16(22)18-14-13(26-17(14)23)8-9-4-6-10(7-5-9)19(24)25/h1-7,13-14,20-21H,8H2,(H,18,22)/t13-,14+/m1/s1 |
| InChI Key | AINNQKIVZOTQBB-KGLIPLIRSA-N |
Properties
| Appearance | Crystalline Solid |
| Antibiotic Activity Spectrum | Bacteria |
| Boiling Point | 644.4±55.0°C at 760 mmHg |
| Density | 1.57 g/cm3 |
| Solubility | Soluble in DMSO, Acetonitrile |
Reference Reading
1. Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion
Hang Qiao, Mingyu Xia, Yiyuan Cheng, Jintong Zhou, Li Zheng, Wei Li, Jing Wang, Pengfei Fang Commun Biol. 2023 Jan 27;6(1):107. doi: 10.1038/s42003-023-04517-7.
Aminoacyl-tRNA synthetases (AARSs), a family of essential protein synthesis enzymes, are attractive targets for drug development. Although several different types of AARS inhibitors have been identified, AARS covalent inhibitors have not been reported. Here we present five unusual crystal structures showing that threonyl-tRNA synthetase (ThrRS) is covalently inhibited by a natural product, obafluorin (OB). The residue forming a covalent bond with OB is a tyrosine in ThrRS active center, which is not commonly modified by covalent inhibitors. The two hydroxyl groups on the o-diphenol moiety of OB form two coordination bonds with the conserved zinc ion in the active center of ThrRS. Therefore, the β-lactone structure of OB can undergo ester exchange reaction with the phenolic group of the adjacent tyrosine to form a covalent bond between the compound and the enzyme, and allow its nitrobenzene structure to occupy the binding site of tRNA. In addition, when this tyrosine was replaced by a lysine or even a weakly nucleophilic arginine, similar bonds could also be formed. Our report of the mechanism of a class of AARS covalent inhibitor targeting multiple amino acid residues could facilitate approaches to drug discovery for cancer and infectious diseases.
2. l-Threonine Transaldolase Activity Is Enabled by a Persistent Catalytic Intermediate
Prasanth Kumar, Anthony Meza, Jonathan M Ellis, Grace A Carlson, Craig A Bingman, Andrew R Buller ACS Chem Biol. 2021 Jan 15;16(1):86-95. doi: 10.1021/acschembio.0c00753. Epub 2020 Dec 18.
l-Threonine transaldolases (lTTAs) are a poorly characterized class of pyridoxal-5'-phosphate (PLP) dependent enzymes responsible for the biosynthesis of diverse β-hydroxy amino acids. Here, we study the catalytic mechanism of ObiH, an lTTA essential for biosynthesis of the β-lactone natural product obafluorin. Heterologously expressed ObiH purifies as a mixture of chemical states including a catalytically inactive form of the PLP cofactor. Photoexcitation of ObiH promotes the conversion of the inactive state of the enzyme to the active form. UV-vis spectroscopic analysis reveals that ObiH catalyzes the retro-aldol cleavage of l-threonine to form a remarkably persistent glycyl quinonoid intermediate, with a half-life of ~3 h. Protonation of this intermediate is kinetically disfavored, enabling on-cycle reactivity with aldehydes to form β-hydroxy amino acids. We demonstrate the synthetic potential of ObiH via the single step synthesis of (2S,3R)-β-hydroxyleucine. To further understand the structural features underpinning this desirable reactivity, we determined the crystal structure of ObiH bound to PLP as the Schiff's base at 1.66 Å resolution. This high-resolution model revealed a unique active site configuration wherein the evolutionarily conserved Asp that traditionally H-bonds to the cofactor is swapped for a neighboring Glu. Molecular dynamics simulations combined with mutagenesis studies indicate that a structural rearrangement is associated with l-threonine entry into the catalytic cycle. Together, these data explain the basis for the unique reactivity of lTTA enzymes and provide a foundation for future engineering and mechanistic analysis.
3. The structural basis of N-acyl-α-amino-β-lactone formation catalyzed by a nonribosomal peptide synthetase
Dale F Kreitler, Erin M Gemmell, Jason E Schaffer, Timothy A Wencewicz, Andrew M Gulick Nat Commun. 2019 Jul 31;10(1):3432. doi: 10.1038/s41467-019-11383-7.
Nonribosomal peptide synthetases produce diverse natural products using a multidomain architecture where the growing peptide, attached to an integrated carrier domain, is delivered to neighboring catalytic domains for bond formation and modification. Investigation of these systems can lead to the discovery of new structures, unusual biosynthetic transformations, and to the engineering of catalysts for generating new products. The antimicrobial β-lactone obafluorin is produced nonribosomally from dihydroxybenzoic acid and a β-hydroxy amino acid that cyclizes into the β-lactone during product release. Here we report the structure of the nonribosomal peptide synthetase ObiF1, highlighting the structure of the β-lactone-producing thioesterase domain and an interaction between the C-terminal MbtH-like domain with an upstream adenylation domain. Biochemical assays examine catalytic promiscuity, provide mechanistic insight, and demonstrate utility for generating obafluorin analogs. These results advance our understanding of the structural cycle of nonribosomal peptide synthetases and provide insights into the production of β-lactone natural products.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
