Methanobactin: a copper binding compound having antibiotic and antioxidant activity isolated from methanotrophic bacteria
View Patent ↗A means and method for treating bacterial infection, providing antioxidant activity, and chelating copper using a copper binding compound produced by methanotrophic bacteria is described. The compound, known as methanobactin, is the first of a new class of antibiotics having gram-positive activity. Methanobactin has been sequenced, and its structural formula determined.
1. An isolated copper binding protein having a sequence selected from the group consisting of N-2-isopropylester-(4-thionyl-5-hydroxy-imidazole)-Gly 1 -Ser 2 -Cys 3 -Tyr 4 -pyrrolidine-(4-thionyl-5-hydroxy-imidazole)-Ser 5 -Cys 6 -Met 7 and N-2-isopropylester-(4-thiocarbonyl-5-hydroxy-imidazolate)-Gly 1 -Ser 2 -Cys 3 -Tyr 4 -pyrrolidine-(4hydroxy-5-thiocarbonyl-imidazolate)-Ser 5 -Cys 6 -Met 7 .
2. The copper binding protein of claim 1 having the following structure:
3. The copper binding protein of claim 1 having the following structure:
4. The copper binding protein of claim 1 that is isolated from a methanotroph.
5. The copper binding protein of claim 1 that is synthetic.
6. A pharmaceutical composition comprising: a copper binding protein methanobactin; and a pharmaceutically acceptable carrier, whereby the methanobactin has a sequence selected from the group consisting of N-2-isopropylester-(4-thionyl-5-hydroxy-imidazole)-Gly 1 -Ser 2 -Cys 3 -Tyr 4 -pyrrolidine-(4-thionyl-5-hydroxy-imidazole)-Ser 5 -Cys 6 -Met 7 and N-2-isopropylester-(4-thiocarbonyl-5-hydroxy-imidazolate)-Gly 1 -Ser 2 -Cys 3 -Tyr 4 -pyrrolidine-(4-hydroxy-5-thiocarbonyl-imidazolate)-Ser 5 -Cys 6 -Met 3 .
7. The pharmaceutical composition of claim 6 whereby the methanobactin has the following structure:
8. The pharmaceutical composition of claim 6 whereby the methanobactin has the following structure:
9. The pharmaceutical composition of claim 6 whereby the methanobactin is isolated from at least one methanotroph that produces both pMMO and sMMO.
10. The pharmaceutical composition of claim 6 whereby the methanobactin is synthetic.
11. The pharmaceutical composition of claim 6 that is suitable for administration by a method selected from the group consisting of oral, subcutaneous, intravenous, intranasal, rectal, sublingual, buccal, and topical.
12. A method of treating a bacterial infection comprising: administering a bacterial treatment effective amount of the copper binding protein of claim 1 .
13. The method of claim 12 wherein the copper binding protein is administered in a dose of between about 0.1–1000 mg/kg/day.
14. The method of claim 13 wherein the copper binding protein is administered in a dose of between about 1–100 mg/kg/day.
15. The method of claim 12 wherein the copper binding protein is administered in a single dose.
16. The method of claim 12 wherein the copper binding protein is administered in divided doses.
17. The method of claim 12 wherein the copper binding protein is administered for a time period of at least 5 days.
18. The method of claim 12 wherein the copper binding protein is administered for treatment of a gram-positive bacterial infection.
19. The method of claim 12 wherein the copper binding protein is co-administered with a metal chelator for treatment of a gram-negative bacterial infection.
20. The method of claim 19 wherein the metal chelator is EDTA.
21. The method of claim 19 whereby the copper binding protein is co-administered with the metal chelator in a molar concentration from about 1:1 to about 5:1 metal chelator to methanobactin.
22. The method of claim 12 whereby the copper binding protein is administered in a pharmaceutically acceptable carrier.
23. A method of inhibiting oxygen radical formation comprising: administering to the animal an oxygen radical formation inhibiting amount of the copper binding protein of claim 1 .
24. The method of claim 23 wherein the copper binding protein is administered in a dose of between about 0.1–1000 mg/kg/day.
25. The method of claim 24 wherein the copper binding protein is administered in a dose of between about 1–100 mg/kg/day.
26. A method of chelating copper comprising: administering a copper-chelating effective amount of the copper binding protein of claim 1 .
27. The method of claim 26 wherein the copper binding protein is administered in a dose of between about 0.1–1000 mg/kg/day.
28. The method of claim 27 wherein the copper binding protein is administered in a dose of between about 1–100 mg/kg/day.