Chuangxinmycin
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| Category | Antibiotics |
| Catalog number | BBF-00334 |
| CAS | 63339-68-4 |
| Molecular Weight | 233.29 |
| Molecular Formula | C12H11NO2S |
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Description
Chuangxinmycin is produced by the strain of Actinoplanes jinanensis. It has activities against Staphylococcus aureus, Haemophilus influenzae, Escherichia coli and Shigella laminae.
Specification
| Synonyms | Chuanghsinmycin; (-)-chuangxinmycin; cis-(-)-3,5-Dihydro-3-methyl-2H-thiopyrano(4,3,2-cd)indole-2-carboxylic acid |
| IUPAC Name | (5S,6R)-5-methyl-7-thia-2-azatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraene-6-carboxylic acid |
| Canonical SMILES | CC1C(SC2=CC=CC3=C2C1=CN3)C(=O)O |
| InChI | InChI=1S/C12H11NO2S/c1-6-7-5-13-8-3-2-4-9(10(7)8)16-11(6)12(14)15/h2-6,11,13H,1H3,(H,14,15)/t6-,11+/m0/s1 |
| InChI Key | DKHFLDXCKWDVMF-UPONEAKYSA-N |
Properties
| Appearance | White or Light Yellow Acicular Crystalline |
| Antibiotic Activity Spectrum | Gram-positive bacteria; fungi |
| Melting Point | 192-192.5 °C |
| Solubility | Soluble in Acetone, Ether and Pyridine |
Reference Reading
1. Structural insights into the specific interaction between Geobacillus stearothermophilus tryptophanyl-tRNA synthetase and antimicrobial Chuangxinmycin
Shuai Fan, Guangxin Lv, Xiao Feng, Guangteng Wu, Yuanyuan Jin, Maocai Yan, Zhaoyong Yang J Biol Chem. 2022 Feb;298(2):101580. doi: 10.1016/j.jbc.2022.101580. Epub 2022 Jan 12.
The potential antimicrobial compound Chuangxinmycin (CXM) targets the tryptophanyl-tRNA synthetase (TrpRS) of both Gram-negative and Gram-positive bacteria. However, the specific steric recognition mode and interaction mechanism between CXM and TrpRS is unclear. Here, we studied this interaction using recombinant GsTrpRS from Geobacillus stearothermophilus by X-ray crystallography and molecular dynamics (MD) simulations. The crystal structure of the recombinant GsTrpRS in complex with CXM was experimentally determined to a resolution at 2.06 Å. After analysis using a complex-structure probe, MD simulations, and site-directed mutation verification through isothermal titration calorimetry, the interaction between CXM and GsTrpRS was determined to involve the key residues M129, D132, I133, and V141 of GsTrpRS. We further evaluated binding affinities between GsTrpRS WT/mutants and CXM; GsTrpRS was found to bind CXM through hydrogen bonds with D132 and hydrophobic interactions between the lipophilic tricyclic ring of CXM and M129, I133, and V141 in the substrate-binding pockets. This study elucidates the precise interaction mechanism between CXM and its target GsTrpRS at the molecular level and provides a theoretical foundation and guidance for the screening and rational design of more effective CXM analogs against both Gram-negative and Gram-positive bacteria.
2. The Cytochrome P450 Catalyzing C-S Bond Formation in S-Heterocyclization of Chuangxinmycin Biosynthesis
Yuanyuan Shi, Zhibo Jiang, Xiaowen Hu, Xiaomin Hu, Renjie Gu, Bingya Jiang, Lijie Zuo, Xingxing Li, Hongmin Sun, Cong Zhang, Lifei Wang, Linzhuan Wu, Bin Hong Angew Chem Int Ed Engl. 2021 Jul 5;60(28):15399-15404. doi: 10.1002/anie.202015814. Epub 2021 Jun 8.
Microbial sulfur-containing secondary metabolites show various biological activities, but the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp2 )-H thiolation by the P450 in chuangxinmycin biosynthesis.
3. Biosynthesis of Chuangxinmycin Featuring a Deubiquitinase-like Sulfurtransferase
Xingwang Zhang, Xiaokun Xu, Cai You, Chaofan Yang, Jiawei Guo, Moli Sang, Ce Geng, Fangyuan Cheng, Lei Du, Yuemao Shen, Sheng Wang, Haidong Lan, Fan Yang, Yuezhong Li, Ya-Jie Tang, Youming Zhang, Xiaoying Bian, Shengying Li, Wei Zhang Angew Chem Int Ed Engl. 2021 Nov 8;60(46):24418-24423. doi: 10.1002/anie.202107745. Epub 2021 Oct 7.
The knowledge on sulfur incorporation mechanism involved in sulfur-containing molecule biosynthesis remains limited. Chuangxinmycin is a sulfur-containing antibiotic with a unique thiopyrano[4,3,2-cd]indole (TPI) skeleton and selective inhibitory activity against bacterial tryptophanyl-tRNA synthetase. Despite the previously reported biosynthetic gene clusters and the recent functional characterization of a P450 enzyme responsible for C-S bond formation, the enzymatic mechanism for sulfur incorporation remains unknown. Here, we resolve this central biosynthetic problem by in vitro biochemical characterization of the key enzymes and reconstitute the TPI skeleton in a one-pot enzymatic reaction. We reveal that the JAMM/MPN+ protein Cxm3 functions as a deubiquitinase-like sulfurtransferase to catalyze a non-classical sulfur-transfer reaction by interacting with the ubiquitin-like sulfur carrier protein Cxm4GG. This finding adds a new mechanism for sulfurtransferase in nature.
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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 ╳
