Ficellomycin
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| Category | Antibiotics |
| Catalog number | BBF-00927 |
| CAS | 59458-27-4 |
| Molecular Weight | 312.37 |
| Molecular Formula | C13H24N6O3 |
| Purity | >98% |
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Description
Ficellomycin is a peptide antibiotic produced by Streptomyces ficellus. Activity against gram-positive bacteria.
Specification
| Synonyms | Antibiotic U 47929 |
| Storage | Store at -20°C |
| IUPAC Name | 2-[(2-amino-3-methylbutanoyl)amino]-2-[4-(diaminomethylideneamino)-1-azabicyclo[3.1.0]hexan-2-yl]acetic acid |
| Canonical SMILES | CC(C)C(C(=O)NC(C1CC(C2N1C2)N=C(N)N)C(=O)O)N |
| InChI | InChI=1S/C13H24N6O3/c1-5(2)9(14)11(20)18-10(12(21)22)7-3-6(17-13(15)16)8-4-19(7)8/h5-10H,3-4,14H2,1-2H3,(H,18,20)(H,21,22)(H4,15,16,17) |
| InChI Key | DGIHWRUPUISVIZ-UHFFFAOYSA-N |
Properties
| Appearance | Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria |
| Density | 1.68 g/cm3 |
| Solubility | Soluble in Methanol, Water, DMSO |
Reference Reading
1. Mechanisms of Sugar Aminotransferase-like Enzymes to Synthesize Stereoisomers of Non-proteinogenic Amino Acids in Natural Product Biosynthesis
Sumire Kurosawa, Hironori Okamura, Ayako Yoshida, Takeo Tomita, Yusuke Sone, Fumihito Hasebe, Tetsuro Shinada, Hirosato Takikawa, Saori Kosono, Makoto Nishiyama ACS Chem Biol. 2023 Feb 17;18(2):385-395. doi: 10.1021/acschembio.2c00823. Epub 2023 Jan 20.
(2,6)-Diamino-(5,7)-dihydroxyheptanoic acid (DADH), a non-proteinogenic amino acid, is converted to 1-azabicyclo[3.1.0]hexane ring-containing amino acids that are subsequently incorporated into ficellomycin and vazabitide A. The present study revealed that the sugar aminotransferase-like enzymes Fic25 and Vzb9, with a high amino acid sequence identity (56%) to each other, synthesized stereoisomers of DADH with (6S) and (6R) configurations, respectively. The crystal structure of the Fic25 complex with a PLP-(6S)-N2-acetyl-DADH adduct indicated that Asn45 and Gln197 (Asn205 and Ala53 in Vzb9) were located at positions that affected the stereochemistry of DADH being synthesized. A modeling study suggested that amino acid substitutions between Fic25 and Vzb9 allowed the enzymes to bind to the substrate with almost 180° rotation in the C5-C7 portions of the DADH molecules, accompanied by a concomitant shift in their C1-C4 portions. In support of this result, the replacement of two corresponding residues in Fic25 and Vzb9 increased (6R) and (6S) stereoselectivities, respectively. The different stereochemistry at C6 of DADH resulted in a different stereochemistry/orientation of the aziridine portion of the 1-azabicyclo[3.1.0]hexane ring, which plays a crucial role in biological activity, between ficellomycin and vazabitide A. A phylogenic analysis suggested that Fic25 and Vzb9 evolved from sugar aminotransferases to produce unusual building blocks for expanding the structural diversity of secondary metabolites.
2. Insight into enzyme-catalyzed aziridine formation mechanism in ficellomycin biosynthesis
Rong Yue, Meng Li, Yue Wang, Ying Guan, Jing Zhang, Zhongli Yan, Fufeng Liu, Fuping Lu, Huitu Zhang Eur J Med Chem. 2020 Oct 15;204:112639. doi: 10.1016/j.ejmech.2020.112639. Epub 2020 Jul 19.
Ficellomycin is an aziridine-containing antibiotic, produced by Streptomyces ficellus. Based on the newly identified ficellomycin gene cluster and the assigned functions of its genes, a possible pathway for aziridine ring formation in ficellomycin was proposed, which is a complex process involving at least 3 enzymatic steps. To obtain support for the proposed mechanism, the targeted genes encoding sulfate adenylyltransferase, adenylsulfate kinase, and a putative sulfotransferase were respectively disrupted and the subsequent analysis of their fermentation products revealed that all the three genes were involved in aziridine formation. To further confirm the mechanism, the key gene encoding a putative sulfotransferase was over expressed in Escherichia coli Rosseta (DE3). Enzyme assays indicated that the expressed sulfotransferase could specifically transfer a sulfo group from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) onto the hydroxyl group of (R)-(-)-2-pyrrolidinemethanol. This introduces a good leaving group in the form of the sulfated hydroxyl moiety, which is then converted into an aziridine ring through an intramolecular nucleophilic attack by the adjacent secondary amine. The sulfation/intramolecular cyclization reaction sequence maybe a general strategy for aziridine biosynthesis in microorganisms. Discovery of this mechanism revealed an enzyme-catalyzed route for the synthesis of aziridine-containing reagents and provided an important insight into the functional diversity of sulfotransferases.
3. Guanidyl modification of the 1-azabicyclo[3.1.0]hexane ring in ficellomycin essential for its biological activity
Sumire Kurosawa, Kenichi Matsuda, Fumihito Hasebe, Taro Shiraishi, Kazuo Shin-Ya, Tomohisa Kuzuyama, Makoto Nishiyama Org Biomol Chem. 2020 Jul 15;18(27):5137-5144. doi: 10.1039/d0ob00339e.
The 1-azabicyclo[3.1.0]hexane ring is a key moiety in natural products for biological activities against bacteria, fungi, and tumor through DNA alkylation. Ficellomycin is a dipeptide that consists of l-valine and a non-proteinogenic amino acid with the 1-azabicyclo[3.1.0]hexane ring structure. Although the biosynthetic gene cluster of ficellomycin has been identified, the biosynthetic pathway currently remains unclear. We herein report the final stage of ficellomycin biosynthesis involving ring modifications and successive dipeptide formation. After the ring is formed, the hydroxy group of the ring is converted into the guanidyl unit by three enzymes, which include an aminotransferase with a novel inter ω-ω amino-transferring activity. In the last step, the resulting 1-azabicyclo[3.1.0]hexane ring-containing amino acid is connected with l-valine by an amino acid ligase to yield ficellomycin. The present study revealed a new machinery that expands the structural and biological diversities of 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 ╳
