Tautomycetin and tautomycetin analog biosynthesis
The present invention relates to the biosynthetic gene cluster for tautomycetin (TTN) produces tautomycetin. Also provided are engineered micro-organisms for the production of TTN and analogs thereof, as well as methods of screening for compounds for activity.
1. An isolated analog of tautomycetin (TTN) having the formula:
wherein X=O, OH or H, and R=(CH) 2 COOH or CH(OH)CH 2 -COOH.
2. The analog of claim 1 , wherein the analog has the structure:
3. The analog of claim 1 , wherein the analog has the structure:
4. The analog of claim 1 , wherein the analog has the structure:
5. The analog of claim 1 , wherein the analog has the structure:
6. A method of producing a compound having the formula:
comprising (a) providing a Streptomyces bacterium comprising an inactivating mutation in the ttnf gene; and (b) incubating said bacterium on conditions sufficient for a wild-type Streptomyces bacterium of the same species to produce tautomycetin.
7. A method of producing a compound having the formula:
wherein X=O, OH or H, comprising (a) providing a Streptomyces bacterium comprising an inactivating mutation in the ttnd gene; and (b) incubating said bacterium on conditions sufficient for a wild-type Streptomyces bacterium of the same species to produce tautomycetin.
8. The method of claim 7 , wherein the compound has the formula:
9. The method of claim 7 , wherein the compound has the formula:
10. The method of claim 7 , wherein the compound has the formula: