Aspergillomarasmine A is an polyamino acid naturally produced by the mold ''

Aspergillus versicolor ''Aspergillus versicolor'' is a slow-growing filamentous fungus commonly found in damp indoor environments and on food products. It has a characteristic musty odor associated with moldy homes and is a major producer of the hepatotoxic and carcin ...

''. The substance has been reported to inhibit two

antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...

carbapenemase Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems ...

proteins in bacteria,

New Delhi metallo-beta-lactamase 1 NDM-1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. The gene f ...

(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 Barley (''Hordeum vulgare''), a member of the grass family, is a major cereal grain grown in temperate climates globally. It was one of the first cultivated grains, particularly in Eurasia as early as 10,000 years ago. Globally 70% of barley pr ...

and other plants, being termed as "Toxin C" when produced by ''

Pyrenophora teres ''Pyrenophora teres'' is a necrotrophic fungal pathogen of some plant species, the most significant of which are economically important agricultural crops such as barley. Toxins include aspergillomarasmine A and related compounds. Host & symptom ...

''. The molecule is a tetra

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

with four -COOH groups. One section of the molecule is the amino acid

aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

. This has two

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...

molecules attached by substituting a hydrogen on the methyl group with a link to the amine group. Aspergillomarasmine B differs in that the last alanine is replaced by

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

. 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 ''

'' 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 A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''. Nomenclature Greek prefixes in alphabetical order indicate ring size: * α-Lactam (3-atom rings) * β-Lacta ...

form (anhydroaspergillomarasmine A) are together termed the marasmines. Other producers of aspergillomarasmine A include ''

Aspergillus flavus ''Aspergillus flavus'' is a saprotrophic and pathogenic fungus with a cosmopolitan distribution. It is best known for its colonization of cereal grains, legumes, and tree nuts. Postharvest rot typically develops during harvest, storage, and/or t ...

'', ''

Aspergillus oryzae ''Aspergillus oryzae'', also known as , is a filamentous fungus (a mold) used in East Asia to saccharify rice, sweet potato, and barley in the making of alcoholic beverages such as ''sake'' and '' shōchū'', and also to ferment soybeans for m ...

'', ''

Colletotrichum gloeosporioides ''Glomerella cingulata'' is a fungal plant pathogen, being the name of the sexual stage (teleomorph) while the more commonly referred to asexual stage (anamorph) is called ''Colletotrichum gloeosporioides''. For most of this article the pathogen ...

'', and ''

Fusarium oxysporum ''Fusarium oxysporum'' (Schlecht as emended by Snyder and Hansen), an ascomycete fungus, comprises all the species, varieties and forms recognized by Wollenweber and Reinking within an infrageneric grouping called section Elegans. It is part of ...

''. In mice the

LD50 In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the ...

toxic dose of aspergillomarasmine A is 159.8 mg/kg.

Properties

Aspergillomarasmine A takes the form of colourless crystals. The chemical is insoluble in common

organic solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for p ...

s, but can dissolve in water under either basic or strongly acidic conditions. Anhydroaspergillomarasmine A, a lactam of aspergillomarasmine A, chemically called -(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 Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with a ...

. Aspergillomarasmine A functions as a

chelating Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a Denticity, polydentate (multiple bonded) ligand and a single central metal atom. These l ...

agent, sequestering Fe³⁺ ions. It can inhibit endothelin converting enzymes even in the live rat, probably by chelating metals required by

metalloprotease A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myogen ...

s. When heated, aspergillomarasmine A decomposes between 225° and 236 °C.

Hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

produces L-

and racemic

2,3-diaminopropionic acid 2,3-Diaminopropionic acid (2,3-diaminopropionate, Dpr) is a non-proteinogenic amino acid found in certain secondary metabolites, including zwittermicin A and tuberactinomycin. Biosynthesis 2,3-Diaminopropionate is formed by the pyridoxal phos ...

. Even though the precursor component is chiral, 2,3-diaminopropionic acid easily racemizes in acid. Aspergillomarasmine A has �sup>20°_D at pH 7 of -48°. With nitrous acid aspergillomarasmine A is deaminated, and

isoserine Isoserine is a non-proteinogenic α-hydroxy-β-amino acid, and an isomer of serine. Non-proteinogenic amino acids do not form proteins, and are not part of the genetic code of any known organism. Isoserine has only been produced synthetically. T ...

with aspartic acid is formed.

Titration Titration (also known as titrimetry and volumetric analysis) is a common laboratory method of quantitative chemical analysis to determine the concentration of an identified analyte (a substance to be analyzed). A reagent, termed the ''titrant'' ...

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. Treatment with

ninhydrin Ninhydrin (2,2-dihydroxyindane-1,3-dione) is an organic compound with the formula C6H4(CO)2C(OH)2. It is used to detect ammonia and amines. Upon reaction with these amines, ninhydrin gets converted into deep blue or purple derivatives, which are ...

shows a purple colour.

References

{{Reflist, 35em Antimicrobial resistance Amino acids