Enterocin

Enterocin
Names
	IUPAC name (10S)-2-benzoyl-1,3,8,10-tetrahydroxy-9-(4-methoxy-6-oxopyran-2-yl)-5-oxatricyclo[4.3.1.03,8]decan-4-one
	Other names Vulgamycin
Identifiers
CAS Number	59678-46-5 ;
3D model (JSmol)	Interactive image;
ChemSpider	19978603;
PubChem CID	10478614;
CompTox Dashboard (EPA)	DTXSID10975078 ;
	InChI InChI=1S/C22H20O10/c1-30-11-7-12(31-14(23)8-11)16-20(27)9-13-18(25)21(16,28)17(22(20,29)19(26)32-13)15(24)10-5-3-2-4-6-10/h2-8,13,16-18,25,27-29H,9H2,1H3/t13?,16?,17?,18-,20?,21?,22?/m0/s1 Key: CTBBEXWJRAPJIZ-LXJDDUSDSA-N;
	SMILES COC1=CC(=O)OC(=C1)C2C3(CC4C(C2(C(C3(C(=O)O4)O)C(=O)C5=CC=CC=C5)O)O)O;
Properties
Chemical formula	C22H20O10
Molar mass	444.392 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

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.^[9]

References

^ Khan H, Flint S, Yu PL (June 2010). "Enterocins in food preservation". International Journal of Food Microbiology. 141 (1–2): 1–10. doi:10.1016/j.ijfoodmicro.2010.03.005. PMID 20399522.
^ Singh A, Walia D, Batra N (2018-01-01). "Fresh-Cut Fruits: Microbial Degradation and Preservation". Microbial Contamination and Food Degradation. pp. 149–176. doi:10.1016/B978-0-12-811515-2.00006-8. ISBN 978-0-12-811515-2.
^ Miyairi N, Sakai H, Konomi T, Imanaka H (March 1976). "Enterocin, a new antibiotic taxonomy, isolation and characterization". The Journal of Antibiotics. 29 (3): 227–35. doi:10.7164/antibiotics.29.227. PMID 770404.
^ 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. doi:10.1021/jo951794g. ISSN 0022-3263.
^ Bonet B, Teufel R, Crüsemann M, Ziemert N, Moore BS (March 2015). "Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin". Journal of Natural Products. 78 (3): 539–42. doi:10.1021/np500664q. PMC 4380194. PMID 25382643.
^ Rizzo A, Trauner D (April 2018). "Toward (-)-Enterocin: An Improved Cuprate Barbier Protocol To Overcome Strain and Sterical Hindrance". Organic Letters. 20 (7): 1841–1844. doi:10.1021/acs.orglett.8b00353. PMID 29553746.
^ Teufel R, Miyanaga A, Michaudel Q, Stull F, Louie G, Noel JP, et al. (November 2013). "Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement". Nature. 503 (7477): 552–556. Bibcode:2013Natur.503..552T. doi:10.1038/nature12643. PMC 3844076. PMID 24162851.
^ Rohr J, Hertweck C (2010-01-01). "Type II PKS". In Liu HW, Mander L (eds.). Comprehensive Natural Products II. pp. 227–303. doi:10.1016/B978-008045382-8.00703-6. ISBN 9780080453828.
^ Kalaitzis JA, Cheng Q, Thomas PM, Kelleher NL, Moore BS (March 2009). "In vitro biosynthesis of unnatural enterocin and wailupemycin polyketides". Journal of Natural Products. 72 (3): 469–72. doi:10.1021/np800598t. PMC 2765504. PMID 19215142.

[1] Khan H, Flint S, Yu PL (June 2010). "Enterocins in food preservation". International Journal of Food Microbiology. 141 (1–2): 1–10. doi:10.1016/j.ijfoodmicro.2010.03.005. PMID 20399522.

[2] Singh A, Walia D, Batra N (2018-01-01). "Fresh-Cut Fruits: Microbial Degradation and Preservation". Microbial Contamination and Food Degradation. pp. 149–176. doi:10.1016/B978-0-12-811515-2.00006-8. ISBN 978-0-12-811515-2.

[3] Miyairi N, Sakai H, Konomi T, Imanaka H (March 1976). "Enterocin, a new antibiotic taxonomy, isolation and characterization". The Journal of Antibiotics. 29 (3): 227–35. doi:10.7164/antibiotics.29.227. PMID 770404.

[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. doi:10.1021/jo951794g. ISSN 0022-3263.

[5] Bonet B, Teufel R, Crüsemann M, Ziemert N, Moore BS (March 2015). "Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin". Journal of Natural Products. 78 (3): 539–42. doi:10.1021/np500664q. PMC 4380194. PMID 25382643.

[6] Rizzo A, Trauner D (April 2018). "Toward (-)-Enterocin: An Improved Cuprate Barbier Protocol To Overcome Strain and Sterical Hindrance". Organic Letters. 20 (7): 1841–1844. doi:10.1021/acs.orglett.8b00353. PMID 29553746.

[7] Teufel R, Miyanaga A, Michaudel Q, Stull F, Louie G, Noel JP, et al. (November 2013). "Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement". Nature. 503 (7477): 552–556. Bibcode:2013Natur.503..552T. doi:10.1038/nature12643. PMC 3844076. PMID 24162851.

[8] Rohr J, Hertweck C (2010-01-01). "Type II PKS". In Liu HW, Mander L (eds.). Comprehensive Natural Products II. pp. 227–303. doi:10.1016/B978-008045382-8.00703-6. ISBN 9780080453828.

[9] Kalaitzis JA, Cheng Q, Thomas PM, Kelleher NL, Moore BS (March 2009). "In vitro biosynthesis of unnatural enterocin and wailupemycin polyketides". Journal of Natural Products. 72 (3): 469–72. doi:10.1021/np800598t. PMC 2765504. PMID 19215142.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]