Brasilicardin A
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| Category | Antibiotics |
| Catalog number | BBF-00171 |
| CAS | |
| Molecular Weight | 893.02 |
| Molecular Formula | C45H68N2O16 |
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Description
Brasilicardin A is a tricyclic diterpene antibiotic produced by Nocardia brasiliensis IFM 0406. It has no antibacterial activity and has an immunosuppressive effect.
Specification
| IUPAC Name | (2S,3S)-4-[(1R,4aS,4bS,6S,7S,8aS,10aS)-6-[(2S,3R,4S,5S,6S)-4-[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-hydroxy-5-(3-hydroxybenzoyl)oxy-6-methyloxan-2-yl]oxy-7-hydroxy-2,4b,8,8,10a-pentamethyl-4,4a,5,6,7,8a,9,10-octahydro-1H-phenanthren-1-yl]-2-amino-3-methoxybutanoic acid |
| Canonical SMILES | CC1C(C(C(C(O1)OC2CC3(C(CCC4(C3CC=C(C4CC(C(C(=O)O)N)OC)C)C)C(C2O)(C)C)C)O)OC5C(C(C(C(O5)CO)O)O)NC(=O)C)OC(=O)C6=CC(=CC=C6)O |
| InChI | InChI=1S/C45H68N2O16/c1-20-12-13-30-44(6,25(20)17-26(58-8)31(46)39(55)56)15-14-29-43(4,5)38(54)27(18-45(29,30)7)60-42-35(53)37(36(21(2)59-42)62-40(57)23-10-9-11-24(50)16-23)63-41-32(47-22(3)49)34(52)33(51)28(19-48)61-41/h9-12,16,21,25-38,41-42,48,50-54H,13-15,17-19,46H2,1-8H3,(H,47,49) |
| InChI Key | SAZHWKBRJJLWKC-YFSQLXLCSA-N |
Properties
| Appearance | White Powder |
Reference Reading
1. Genetic Engineering in Combination with Semi-Synthesis Leads to a New Route for Gram-Scale Production of the Immunosuppressive Natural Product Brasilicardin A
Alma Botas, Michael Eitel, Paul N Schwarz, Anina Buchmann, et al. Angew Chem Int Ed Engl. 2021 Jun 7;60(24):13536-13541. doi: 10.1002/anie.202015852. Epub 2021 May 1.
Brasilicardin A (1) consists of an unusual anti/syn/anti-perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre-clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low-yielding fermentation process using a pathogenic organism and an elaborate, multi-step total synthesis. Our semi-synthetic approach included a) the heterologous expression of the brasilicardin A gene cluster in different non-pathogenic bacterial strains producing brasilicardin A aglycone (5) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardin A (1 a) via a short and straightforward five-steps synthetic route. Additionally, we report the first preclinical data for brasilicardin A.
2. Selective mono-de-O-acetylation of the per-O-acetylated brasilicardin carbohydrate side chain
Michael Eitel, Dhafer S Zinad, Dieter Schollmeyer, Harald Gross, Pierre Koch Carbohydr Res. 2021 Jun;504:108312. doi: 10.1016/j.carres.2021.108312. Epub 2021 Apr 13.
Methanol dried over powdered 4 Å molecular sieves can be used for a selective mono-de-O-acetylation of the phenolic acetyl group of the per-O-acetyl protected brasilicardin A carbohydrate side chain. This reaction opens a practical procedure for a synthetic access to derivates of the immunosuppressive and cytotoxic natural product brasilicardin A.
3. A novel LysR-type regulator negatively affects biosynthesis of the immunosuppressant brasilicardin
Marcin Wolański, Michał Krawiec, Paul N Schwarz, Evi Stegmann, Wolfgang Wohlleben, Anina Buchmann, Harald Gross, Michael Eitel, Pierre Koch, Alma Botas, Carmen Méndez, Luz Elena Núñez, Francisco Morís, Jesus Cortés, Jolanta Zakrzewska-Czerwińska Eng Life Sci. 2020 Nov 4;21(1-2):4-18. doi: 10.1002/elsc.202000038. eCollection 2021 Jan.
Brasilicardin A (BraA) is a promising immunosuppressive compound produced naturally by the pathogenic bacterium Nocardia terpenica IFM 0406. Heterologous host expression of brasilicardin gene cluster showed to be efficient to bypass the safety issues, low production levels and lack of genetic tools related with the use of native producer. Further improvement of production yields requires better understanding of gene expression regulation within the BraA biosynthetic gene cluster (Bra-BGC); however, the only so far known regulator of this gene cluster is Bra12. In this study, we discovered the protein LysRNt, a novel member of the LysR-type transcriptional regulator family, as a regulator of the Bra-BGC. Using in vitro approaches, we identified the gene promoters which are controlled by LysRNt within the Bra-BGC. Corresponding genes encode enzymes involved in BraA biosynthesis as well as the key Bra-BGC regulator Bra12. Importantly, we provide in vivo evidence that LysRNt negatively affects production of brasilicardin congeners in the heterologous host Amycolatopsis japonicum. Finally, we demonstrate that some of the pathway related metabolites, and their chemical analogs, can interact with LysRNt which in turn affects its DNA-binding activity.
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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 ╳
