Bioabsorbable polymer containing 2-hydroxyacid monomers
View Patent ↗Genetically engineered organisms for production of PHA copolymers containing 2-hydroxyacid monomers and the methods of making and using thereof have been developed. The copolymers containing 2-hydroxyacid monomers can be synthesized via biosynthesis by the action of a PHA polymerase in a living cell. By changing the genetic background of the cells, one can control specific metabolic pathways allowing control of the level of glycolic acid co-monomer in the PHA polymer.
1. A method of producing a glycolic acid-containing polyhydroxyalkanoate polymer comprising
Providing a feedstock comprising glycolic acid, 1,4-butane dial, 4-hydroxybutyric acid, or combinations thereof to bacteria expressing a polyhydroxyalkanoate (PHA) synthase and at least one enzyme selected from the group consisting of acetoacetyl-CoA reductases and beta-ketoacyl-CoA thiolases and at least one enzyme for the production of glycolyl-CoA selected from the group consisting of aldehyde dehydrogenase, diol oxidoreductase, enoyl-CoA dehydrase, beta acyl-CoA dehydrogenase, thiolases, and acyl-CoA transferase,
to produce the glycolic acid-containing polyhydroxyalkanoate polymer.
2. The method of claim 1 wherein the PHA synthase is a synthase of poly(3-hydroxyalkanoate) or poly(4-hydroxyalkanaote).
3. The method of claim 1 wherein the PHA synthase is poly(3-hydroxyalkanoate) synthase.
4. The method of claim 1 wherein the PHA synthase is poly(4-hydroxyalkanoate) synthase.
5. The method of claim 4 wherein the PHA synthase is poly(4-hydroxybutyrate) synthase.
6. The method of claim 1 wherein the bacteria is E. coli.
7. The method of claim 1 wherein the bacteria is E. coli having mutations selected from fadR601 and atoC constitutive mutations.
8. The method of claim 1 wherein the aldehyde dehydrogenase is from E. coli , wherein the diol oxidoreductase is from Klebsiella pneumoniae , and wherein the acyl-CoA transferase is from Clostridium kluyveri.
9. The method of claim 1 comprising feeding 1,4-butanediol and glucose to the bacteria.
10. The method of claim 1 comprising feeding glycolic acid to the bacteria.
11. The method of claim 1 comprising feeding 4-hydroxybutyric acid to the bacteria.