Enterocin Explained

Enterocin and its derivatives are bacteriocins synthesized by the lactic acid bacteria, Enterococcus. This class of polyketide antibiotics are effective against foodborne pathogens including L. monocytogenes, Listeria, and Bacillus.^[1] Due to its proteolytic degradability in the gastrointestinal tract, enterocin is used for controlling foodborne pathogens via human consumption.^[2]

History

Enterocin was discovered from soil and marine Streptomyces^[3] strains as well as from marine ascidians of Didemnum^[4] and it has also been found in a mangrove strains Streptomyces qinglanensis and Salinispora pacifica.^[5]

Total synthesis

The total synthesis of enterocin has been reported.^[6]

Biosynthesis

Enterocin has a caged, tricyclic, nonaromatic core and its formation undergoes a flavoenzyme (EncM) catalyzed Favorskii-like rearrangement of a poly(beta-carbonyl).^[7] 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 or activation of benzoic acid followed by the EncM catalyzed rearrangement.

The enzyme EncN catalyzes the ATP-dependent transfer of the benzoate to EncC, the acyl carrier protein. EncC transfers the aromatic unit to EncA-EncB, the ketosynthase in order for malonation via FabD, the malonyl-CoA:ACP transacylase. A Claisen condensation 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 hydroxylase, EncR yields enterocin.^[8]

Notes and References

1. Khan H, Flint S, Yu PL . Enterocins in food preservation . International Journal of Food Microbiology . 141 . 1–2 . 1–10 . June 2010 . 20399522 . 10.1016/j.ijfoodmicro.2010.03.005 .
2. Book: Singh A, Walia D, Batra N . 2018-01-01 . Fresh-Cut Fruits: Microbial Degradation and Preservation . Microbial Contamination and Food Degradation . 149–176. 10.1016/B978-0-12-811515-2.00006-8 . 978-0-12-811515-2 .
3. Miyairi N, Sakai H, Konomi T, Imanaka H . Enterocin, a new antibiotic taxonomy, isolation and characterization . The Journal of Antibiotics . 29 . 3 . 227–35 . March 1976 . 770404 . 10.7164/antibiotics.29.227 . free .
4. Kang H, Jensen PR, Fenical W . 1996. Isolation of Microbial Antibiotics from a Marine Ascidian of the GenusDidemnum. The Journal of Organic Chemistry. 61. 4. 1543–1546. 10.1021/jo951794g. 0022-3263.
5. Bonet B, Teufel R, Crüsemann M, Ziemert N, Moore BS . Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin . Journal of Natural Products . 78 . 3 . 539–42 . March 2015 . 25382643 . 4380194 . 10.1021/np500664q .
6. Rizzo A, Trauner D . Toward (-)-Enterocin: An Improved Cuprate Barbier Protocol To Overcome Strain and Sterical Hindrance . Organic Letters . 20 . 7 . 1841–1844 . April 2018 . 29553746 . 10.1021/acs.orglett.8b00353 .
7. Teufel R, Miyanaga A, Michaudel Q, Stull F, Louie G, Noel JP, Baran PS, Palfey B, Moore BS . 6 . Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement . Nature . 503 . 7477 . 552–556 . November 2013 . 24162851 . 3844076 . 10.1038/nature12643 . 2013Natur.503..552T .
8. Kalaitzis JA, Cheng Q, Thomas PM, Kelleher NL, Moore BS . In vitro biosynthesis of unnatural enterocin and wailupemycin polyketides . Journal of Natural Products . 72 . 3 . 469–72 . March 2009 . 19215142 . 2765504 . 10.1021/np800598t .