Enterocin and its derivatives are

bacteriocin Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ...

s synthesized by the lactic acid bacteria, ''

Enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical charac ...

''. This class of

polyketide Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...

s are effective against foodborne pathogens including ''

L. monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a Facultative anaerobic organism, facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can gro ...

Listeria ''Listeria'' is a genus of bacteria that acts as an intracellular parasite in mammals. Until 1992, 17 species were known, each containing two subspecies. By 2020, 21 species had been identified. The genus is named in honour of the British pi ...

,'' and ''

Bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum '' Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-shaped bacteria; and the plural ''Bacil ...

.'' Due to its proteolytic degradability in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

, enterocin is used for controlling foodborne pathogens via human consumption.

History

Enterocin was discovered from soil and marine ''

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, ...

'' strains as well as from marine ascidians of ''

Didemnum ''Didemnum'' is a genus of colonial tunicates in the family Didemnidae. It is the most speciose genus in the didemnid family. Species in this genus often have small calcareous spicules embedded in the tunic and form irregular or lobed colonies. S ...

'' and it has also been found in a mangrove strains '' Streptomyces qinglanensis'' and '' Salinispora pacifica''.

Total synthesis

The

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

of enterocin has been reported.

Biosynthesis

Enterocin has a caged, tricyclic,

nonaromatic In chemistry, aromaticity is a chemical property of cyclic (ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satura ...

core and its formation undergoes a flavoenzyme (EncM) catalyzed Favorskii-like rearrangement of a poly(beta-carbonyl). Studies done on enterocin have shown that it is biosynthesized from a type II polyketide synthase (PKS) pathway, starting with a structure derived from

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

or activation of

benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, w ...

followed by the EncM catalyzed rearrangement. Enterocin biosynthesis

The

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

EncN catalyzes the

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

-dependent transfer of the benzoate to EncC, the

acyl carrier protein The acyl carrier protein (ACP) is a cofactor of both fatty acid and polyketide biosynthesis machinery. It is one of the most abundant proteins in cells of ''E. coli.'' In both cases, the growing chain is bound to the ACP via a thioester derived fro ...

. EncC transfers the aromatic unit to EncA-EncB, the

ketosynthase Ketoacyl synthases (KSs) catalyze the condensation reaction of acyl-CoA or acyl-acyl ACP with malonyl-CoA to form 3-ketoacyl-CoA or with malonyl-ACP to form 3-ketoacyl-ACP. This reaction is a key step in the fatty acid synthesis cycle, as the result ...

in order for malonation via FabD, the

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and com ...

:ACP transacylase. A

Claisen condensation The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β- diketone. It is named after Ra ...

occurs between the benzoyl and malonyl groups and occurs six more times followed by reaction with EncD, a ketoreductase; the intermediate undergoes the EncM catalyzed oxidative rearrangement to form the enterocin tricyclic core. Further reaction with ''O''-methyltransferase, EncK and

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

hydroxylase, EncR yields enterocin.

References

{{reflist Antibiotics Oxygen heterocycles Lactones Heterocyclic compounds with 3 rings Methoxy compounds