Fosfazinomycin A
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| Category | Antibiotics |
| Catalog number | BBF-01437 |
| CAS | |
| Molecular Weight | 453.43 |
| Molecular Formula | C15H32N7O7P |
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Description
Fosfazinomycin A is produced by the strain of Streptomyces lavendofoliae. It has the activity of resisting plant pathogenic fungi such as Xanthomonas oryzae.
Properties
| Appearance | Hygroscopic Powder |
| Antibiotic Activity Spectrum | fungi |
| Melting Point | 157-161°C |
Reference Reading
1. Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin
Kwo-Kwang A Wang, Tai L Ng, Peng Wang, Zedu Huang, Emily P Balskus, Wilfred A van der Donk Nat Commun. 2018 Sep 11;9(1):3687. doi: 10.1038/s41467-018-06083-7.
Fosfazinomycin and kinamycin are natural products that contain nitrogen-nitrogen (N-N) bonds but that are otherwise structurally unrelated. Despite their considerable structural differences, their biosynthetic gene clusters share a set of genes predicted to facilitate N-N bond formation. In this study, we show that for both compounds, one of the nitrogen atoms in the N-N bond originates from nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine biosynthetic synthon is generated first and then funneled via a glutamyl carrier into the respective biosynthetic pathways. Therefore, unlike other pathways to N-N bond-containing natural products wherein the N-N bond is formed directly on a biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin, and related compounds, the N-N bond is made in an independent pathway that forms a branch of a convergent route to structurally complex natural products.
2. New Insights into the Biosynthesis of Fosfazinomycin
Zedu Huang, Kwo-Kwang Abraham Wang, Wilfred A van der Donk Chem Sci. 2016;7(8):5219-5223. doi: 10.1039/C6SC01389A. Epub 2016 May 6.
The biosynthetic origin of a unique hydrazide moiety in the phosphonate natural product fosfazinomycin is unknown. This study presents the activities of five proteins encoded in its gene cluster. The flavin dependent oxygenase FzmM catalyses the oxidation of L-Asp to N-hydroxy-Asp. When FzmL is added, fumarate is produced in addition to nitrous acid. The adenylosuccinate lyase homolog FzmR eliminates acetylhydrazine from N-acetylhydrazinosuccinate, which in turn is the product of FzmQ-catalysed acetylation of hydrazinosuccinate. Collectively, these findings suggest a path to N-acetylhydrazine from L-Asp. The incorporation of nitrogen from L-Asp into fosfazinomycin was confirmed by isotope labelling studies. Installation of the N-terminal Val of fosfazinomycin is catalysed by FzmI in a Val-tRNA dependent process.
3. Characterization of a Nitro-Forming Enzyme Involved in Fosfazinomycin Biosynthesis
Hannah Valentino, Pablo Sobrado Biochemistry. 2021 Sep 28;60(38):2851-2864. doi: 10.1021/acs.biochem.1c00512. Epub 2021 Sep 13.
N-hydroxylating monooxygenases (NMOs) are a subclass of flavin-dependent enzymes that hydroxylate nitrogen atoms. Recently, unique NMOs that perform multiple reactions on one substrate molecule have been identified. Fosfazinomycin M (FzmM) is one such NMO, forming nitrosuccinate from aspartate (Asp) in the fosfazinomycin biosynthetic pathway in some Streptomyces sp. This work details the biochemical and kinetic analysis of FzmM. Steady-state kinetic investigation shows that FzmM performs a coupled reaction with Asp (kcat, 3.0 ± 0.01 s-1) forming nitrosuccinate, which can be converted to fumarate and nitrite by the action of FzmL. FzmM displays a 70-fold higher kcat/KM value for NADPH compared to NADH and has a narrow optimal pH range (7.5-8.0). Contrary to other NMOs where the kred is rate-limiting, FzmM exhibits a very fast kred (50 ± 0.01 s-1 at 4 °C) with NADPH. NADPH binds at a KD value of ~400 μM, and hydride transfer occurs with pro-R stereochemistry. Oxidation of FzmM in the absence of Asp exhibits a spectrum with a shoulder at ~370 nm, consistent with the formation of a C(4a)-hydroperoxyflavin intermediate, which decays into oxidized flavin and hydrogen peroxide at a rate 100-fold slower than the kcat. This reaction is enhanced in the presence of Asp with a slightly faster kox than the kcat, suggesting that flavin dehydration or Asp oxidation is partially rate limiting. Multiple sequence analyses of FzmM to NMOs identified conserved residues involved in flavin binding but not for NADPH. Additional sequence analysis to related monooxygenases suggests that FzmM shares sequence motifs absent in other NMOs.
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Bio Calculators
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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
