(R-(R*,R*))-N-(2-((2-Amino-2-carboxyethyl)amino)-2-carboxyethyl)-L-aspartic acid
3D model (JSmol)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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. Aspergillomarasmine A is toxic to leaves of barley and other plants, being termed as "Toxin C" when produced by Pyrenophora teres.
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[contradictory] 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.
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. This precursor, aspergillomarasmine A itself, and a lactam form (anhydroaspergillomarasmine A) are together termed the marasmines.
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. The lactam can be hydrolyzed to aspergillomarasmine A by treating it with trifluoroacetic acid.
Aspergillomarasmine A functions as a chelating agent, sequestering Fe3+ ions. It can inhibit endothelin converting enzymes even in the live rat, probably by chelating metals required by metalloproteases.
- 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.