Aspergillomarasmine A

Aspergillomarasmine A
Names
	IUPAC name (R-(R,R))-N-(2-((2-Amino-2-carboxyethyl)amino)-2-carboxyethyl)-L-aspartic acid
Identifiers
CAS Number	3484-65-9 ;
3D model (JSmol)	Interactive image;
ChemSpider	170641;
PubChem CID	197028;
UNII	K4F9BJQ6EG;
CompTox Dashboard (EPA)	DTXSID60956312 ;
	InChI InChI=1S/C10H17N3O8/c11-4(8(16)17)2-12-6(10(20)21)3-13-5(9(18)19)1-7(14)15/h4-6,12-13H,1-3,11H2,(H,14,15)(H,16,17)(H,18,19)(H,20,21)/t4-,5+,6-/m1/s1 Key: XFTWUNOVBCHBJR-NGJCXOISSA-N;
	SMILES C(C(C(=O)O)NCC(C(=O)O)NCC(C(=O)O)N)C(=O)O;
Properties
Chemical formula	C10H17N3O8
Molar mass	307.257
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	Infobox references

Aspergillomarasmine A is an polyamino acid naturally produced by the mold Aspergillus versicolor. The substance has been reported to inhibit two antibiotic resistance carbapenemase proteins in bacteria, New Delhi metallo-beta-lactamase 1 (NDM-1) and Verona integron-encoded metallo-beta-lactamase (VIM-2), and make those antibiotic-resistant bacteria susceptible to antibiotics.[1] Aspergillomarasmine A is toxic to leaves of barley and other plants, being termed as "Toxin C" when produced by Pyrenophora teres.[2]

The molecule is a tetracarboxylic acid with four -COOH groups. One section of the molecule is the amino acid aspartic acid. This has two alanine molecules attached. Aspergillomarasmine B differs in that the last alanine is replaced by glycine.

The crystalline substance was first isolated in 1956, but its name was given until 1965.[3]

In addition to Aspergillus versicolor, aspergillomarasmine A is also produced by the ascomycete Pyrenophora teres where it acts as a toxin in the barley net-spot blotch disease. In P. teres, a biosynthetic precursor of aspergillomarasmine A, L,L-N-(2-amino-2-carboxyethyl)-aspartic acid has also been isolated and found to contribute to the phytotoxic properties of this microbe.[4] This precursor, aspergillomarasmine A itself, and a lactam form (anhydroaspergillomarasmine A) are together termed the marasmines.[2]

Other producers of aspergillomarasmine A include Aspergillus flavus,[3] Aspergillus oryzae,[5] Colletotrichum gloeosporioides, and Fusarium oxysporum.[2]

In mice the LD50 toxic dose of aspergillomarasmine A is 159.8 mg/kg.[6]

Properties

Aspergillomarasmine A takes the form of colourless crystals. The chemical is insoluble in common organic solvents, but can dissolve in water under either basic or strongly acidic conditions.[3]

Anhydroaspergillomarasmine A, a lactam of aspergillomarasmine A, chemically called [1-(2-amino-2carboxyethyl)-6-carboxy-3-carboxymethyl-3-piperazinone], can also be found in Pyrenophora teres. The relative amount of these two toxins is dependent upon the pH of the growth medium, with lower pH favouring the lactam form.[2] The lactam can be hydrolyzed to aspergillomarasmine A by treating it with trifluoroacetic acid.[2]

Aspergillomarasmine A functions as a chelating agent, sequestering Fe³⁺ ions.[7] It can inhibit endothelin converting enzymes even in the live rat, probably by chelating metals required by metalloproteases.[8]

When heated, aspergillomarasmine A decomposes between 225° and 236 °C. Hydrolysis produces L-aspartic acid and racemic 2,3-diamino-propionic acid. [α]^20°_D at pH 7 is -48°.[3]

With nitrous acid aspergillomarasmine A is deaminated, and isoserine with aspartic acid is formed.[3]

Titration reveals changes in ionisation at pK 3.5 and 4.5 due to carboxylic acid groups, and pK 9.5 and 10 due to amino groups.[3]

Treatment with ninhydrin shows a purple colour.[3]

gollark: Oh, right, array indexing.

gollark: ```python# parsita-based pseudocode syntax parserfrom stmt import *from parsita import *from parsita.util import constantdef compose(f, g): return lambda x: f(g(x))def map_expr(x): start, end = x if end == "": return start return Op([start, end[1]], end[0])def map_unop_expr(x): return Op(x[1], x[0])def aliases(name, aliases): p = lit(name) for alias in aliases: p |= (lit(alias) > (lambda _: name)) return pclass ExprParser(TextParsers): ε = lit("") IntLit = reg("\-?[0-9]+") > compose(IntLit, int) StrLit = "'" >> reg("[^']*") << "'" > StrLit # TODO escapes (not in "spec" but could be needed) FloatLit = reg("\-?[0-9]+\.[0-9]+") > compose(FloatLit, float) Identifier = reg("[a-zA-Z_]+[a-zA-Z_0-9]*") > Var BracketedExpr = "(" >> Expr << ")" UnaryOperator = lit("NOT") Start = FloatLit | StrLit | IntLit | BracketedExpr | (UnaryOperator & Expr > map_unop_expr) | Identifier # avoid left recursion problems by not doing left recursion # AQA pseudocode does not appear to have a notion of "operator precedence", simplifying parsing logic nicely BinaryOperator = aliases("≤", ["<="]) | aliases("≠", ["!="]) | aliases("≥", [">="]) | lit("DIV") | lit("MOD") | lit("AND") | lit("OR") | reg("[+/*\-=<>]") End = (BinaryOperator & Expr) | ε Expr = (Start & End) > map_exprparse = ExprParser.Expr.parsex = parse("1+2+3 != 6 AND NOT 4 AND x + y")if isinstance(x, Failure): print(x.message)else: print(x.value)```

gollark: <@332271551481118732> Expression parsing is done, I think.

gollark: I wonder if AQA pseudocode *does* have operator precedence. We may need to harvest exam papers.

gollark: This will allow 3% more efficient harnessing of character set anomalies.

References

King, Andrew M.; Sarah A. Reid-Yu; Wenliang Wang; Dustin T. King; Gianfranco De Pascale; Natalie C. Strynadka; Timothy R. Walsh; Brian K. Coombes; Gerard D. Wright (2014). "Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance". Nature. 510 (7506): 503–506. Bibcode:2014Natur.510..503K. doi:10.1038/nature13445. ISSN 0028-0836. PMC 4981499. PMID 24965651.
Weiergang, I.; H.J. Lyngs Jørgensen; I.M. Møller; P. Friis; V. Smedegaard-Petersen (2002). "Optimization of in vitro growth conditions of Pyrenophora teres for production of the phytotoxin aspergillomarasmine A". Physiological and Molecular Plant Pathology. 60 (3): 131–140. doi:10.1006/pmpp.2002.0383. ISSN 0885-5765.
Haenni, A. L.; M. Robert; W. Vetter; L. Roux; M. Barbier; E. Lederer (1965). "Structure chimique des aspergillomarasmines A et B (Chemical structure of aspergellomarasmines A and B)". Helvetica Chimica Acta (in French). 48 (4): 729–750. doi:10.1002/hlca.19650480409. ISSN 0018-019X. PMID 14321962.
Friis, P; Olsen C.E.; Møller B.L. (15 July 1991). "Toxin production in Pyrenophora teres, the ascomycete causing the net-spot blotch disease of barley (Hordeum vulgare L.)". The Journal of Biological Chemistry. 266 (20): 13329–13335. PMID 2071605.
Wagman, G.H.; Cooper, R. (1988-12-01). Natural Products Isolation: Separation Methods for Antimicrobials, Antivirals and Enzyme Inhibitors. Elsevier. p. 499. ISBN 9780080858487. Retrieved 27 June 2014.
Matsuura, Akihiro; Hiroshi Okumura; Rieko Asakura; Naoki Ashizawa; Mayumi Takahashi; Fujio Kobayashi; Nami Ashikawa; Koshi Arai (1993). "Pharmacological profiles of aspergillomarasmines as endothelin converting enzyme inhibitors". The Japanese Journal of Pharmacology. 63 (2): 187–193. doi:10.1254/jjp.63.187. PMID 8283829.
Barbier, M. (1987). "Remarks on the biological activity of aspergillomarasmine A Fe³⁺ chelate and other iron transporting phytotoxins with reference to their role in the photodegradation of aromatic amino-acids in infected plant leaves". Journal of Phytopathology. 120 (4): 365–368. doi:10.1111/j.1439-0434.1987.tb00500.x. ISSN 0931-1785.
Huggins, John P.; Pelton, John T. (1996-12-23). Endothelins in Biology and Medicine. CRC Press. p. 121. ISBN 9780849369759. Retrieved 27 June 2014.

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[King2014-1] King, Andrew M.; Sarah A. Reid-Yu; Wenliang Wang; Dustin T. King; Gianfranco De Pascale; Natalie C. Strynadka; Timothy R. Walsh; Brian K. Coombes; Gerard D. Wright (2014). "Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance". Nature. 510 (7506): 503–506. Bibcode:2014Natur.510..503K. doi:10.1038/nature13445. ISSN 0028-0836. PMC 4981499. PMID 24965651.

[Weiergang2002-2] Weiergang, I.; H.J. Lyngs Jørgensen; I.M. Møller; P. Friis; V. Smedegaard-Petersen (2002). "Optimization of in vitro growth conditions of Pyrenophora teres for production of the phytotoxin aspergillomarasmine A". Physiological and Molecular Plant Pathology. 60 (3): 131–140. doi:10.1006/pmpp.2002.0383. ISSN 0885-5765.

[Haenni1965-3] Haenni, A. L.; M. Robert; W. Vetter; L. Roux; M. Barbier; E. Lederer (1965). "Structure chimique des aspergillomarasmines A et B (Chemical structure of aspergellomarasmines A and B)". Helvetica Chimica Acta (in French). 48 (4): 729–750. doi:10.1002/hlca.19650480409. ISSN 0018-019X. PMID 14321962.

[Friis-4] Friis, P; Olsen C.E.; Møller B.L. (15 July 1991). "Toxin production in Pyrenophora teres, the ascomycete causing the net-spot blotch disease of barley (Hordeum vulgare L.)". The Journal of Biological Chemistry. 266 (20): 13329–13335. PMID 2071605.

[WagmanCooper1988-5] Wagman, G.H.; Cooper, R. (1988-12-01). Natural Products Isolation: Separation Methods for Antimicrobials, Antivirals and Enzyme Inhibitors. Elsevier. p. 499. ISBN 9780080858487. Retrieved 27 June 2014.

[Matsuura-6] Matsuura, Akihiro; Hiroshi Okumura; Rieko Asakura; Naoki Ashizawa; Mayumi Takahashi; Fujio Kobayashi; Nami Ashikawa; Koshi Arai (1993). "Pharmacological profiles of aspergillomarasmines as endothelin converting enzyme inhibitors". The Japanese Journal of Pharmacology. 63 (2): 187–193. doi:10.1254/jjp.63.187. PMID 8283829.

[Barbier1987-7] Barbier, M. (1987). "Remarks on the biological activity of aspergillomarasmine A Fe³⁺ chelate and other iron transporting phytotoxins with reference to their role in the photodegradation of aromatic amino-acids in infected plant leaves". Journal of Phytopathology. 120 (4): 365–368. doi:10.1111/j.1439-0434.1987.tb00500.x. ISSN 0931-1785.

[HugginsPelton1996-8] Huggins, John P.; Pelton, John T. (1996-12-23). Endothelins in Biology and Medicine. CRC Press. p. 121. ISBN 9780849369759. Retrieved 27 June 2014.