Antimycins are produced as secondary metabolites by ''

Streptomyces ''Streptomyces'' is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of ''Streptomyces'' bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, ...

'' bacteria, a soil bacteria. These specialized metabolites likely function to kill neighboring organisms in order to provide the streptomyces bacteria with a competitive edge.

Chemical structures

Biosynthesis

Antimycins are produced by a non-ribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) assembly complex which acts as an assembly line for antimycin production. The assembly is genetically coded for by the ant gene family. The assembly requires 14 proteins, AntBCDEFGHIJKLMNO, which shuttle the intermediates along the assembly line through a series of transesterifications, keto reductions, thiolations (addition of a sulfur containing group), condensations, an
adenylations
The last two steps involving AntB and AntO are tailoring steps. The following steps describe chemically what the Ant Enzymes do in order to synthesize Antimycin. Synthesis begins with tryptophan, an amino acid. 1. The

indole ring Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment ...

of tryptophan, an amino acid, is opened by a pathway-specific tryptophan-2.3-dioxygnease, AntN, to make N-formyl-L-kynurenine. 2. N-formyl-L-kynurenine is converted to

anthranilate Anthranilic acid is an aromatic acid with the formula C6H4(NH2)(CO2H) and has a sweetish taste. The molecule consists of a benzene ring, ''ortho''-substituted with a carboxylic acid and an amine. As a result of containing both acidic and basic ...

by the pathway-specific kynureninase, AntP. 3. Anthranilate is activated by the

acyl-CoA Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this way ...

ligase protein, AntF and loaded onto its cognate carrier protein, AntG, for further processing. 4. Anthranilate is converted to 3-aminosalicylate by a multicomponent

oxygenase An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it. The oxygenases form a class of oxidoreductases; their EC number is EC 1.13 or EC 1.14. Discoverers Oxygenases were disco ...

, AntHIJKL. 5. 3-Aminosalicylate is presented to the NRPS, AntC. AntC has two modules which are organized Condensation1 (C1) -Adenylation1 (A1) -Thiolation1 (T1) -Condensation2 (C2) -Adenylation2 (A2) -Ketoreduction (KR) -Thiolation2 (T2). The A1 domain activates and loads threonine, an amino acid, onto T1, followed by a C1 promoted condensation of 3-aminosalicylate and threonine. The A2 domain activates and loads

pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic aci ...

onto T2. Pyruvate is reduced by the KR domain and condensed with threonine by C2 6. The Ketosynthase domain of PKS catalyses the

decarboxylative condensation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...

between the aminoacyl

thioester In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by t ...

attached to AntC T2 domain and the 2-carboxy-acyl moiety attached to AntD Acetyl Carrier Protein domain. 7. AntM catalyses the reduction of the β-keto group, which precedes the AntD TE domain – promoted release of the nine-membered

dilactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

8. A lipase homologue, AntO, and

acyltransferase Acyltransferase is a type of transferase enzyme that acts upon acyl groups. Examples include: * Glyceronephosphate O-acyltransferase * Lecithin-cholesterol acyltransferase *Long-chain-alcohol O-fatty-acyltransferase In enzymology, a long-chain- ...

homologue, AntB, catalyze the installation of the N-formyl group and the transesterification of the C-8 hydroxyl group, respectively, resulting in the backbone for the Antimycin family.

References

{{reflist Secondary metabolites Antibiotics

Chemical structures

Biosynthesis

See also

References