Methods and microorganisms for making 1,4-butanediol and derivatives thereof from C1 carbons
Genetically modified microorganisms that have the ability to convert carbon substrates into chemical products such as 1,4-BDO are disclosed. For example, genetically modified methanotrophs that are capable of generating 1,4-BDO at high titers from a methane source are disclosed. Methods of making these genetically modified microorganisms and methods of using them are also disclosed.
1. A genetically modified microorganism from the genus Methylcoccus , wherein said microorganism: comprises an overexpressed heterologous gene encoding isocitrate dehydrogenase (icdA); and converts a C1 carbon source to 1,4-butanediol.
2. The genetically-modified microorganism of claim 1 , further comprising a heterologous gene encoding α-ketoglutarate decarboxylase (kgd), 4-hydroxybutyrate dehydrogenase (4hbD), 4-hydroxybutyryl-CoA transferase (Cat2), aldehyde dehydrogenase (Ald), or alcohol dehydrogenase (Adh).
3. The genetically-modified microorganism of claim 1 , further comprising a heterologous gene encoding succinyl-CoA synthetase (SucC), CoA-dependent succinate semialdehyde dehydrogenase (SucD), 4-hydroxybutyrate dehydrogenase (4hbD), 4-hydroxybutyryl-CoA transferase (Cat2), aldehyde dehydrogenase (Ald) or alcohol dehydrogenase (Adh).
4. The genetically modified microorganism of claim 1 , Further comprising a heterologous gene encoding pyruvate dehydrogenase (aceEF), citrate synthase (gltA), and/or aconitate hydratase 1 (acnA).
5. A method of making the genetically modified microorganism of claim 1 , the method comprising contacting a microorganism with a nucleic acid expressing isocitrate dehydrogenase (icdA).
6. A method of making 1,4-butanediol, the method comprising:
a) contacting a C1 carbon with the genetically modified microorganism of claim 1 ; and
b) growing the microorganism to produce the 1,4-butanediol.
7. The method of claim 6 , wherein the C1 carbon is CH 4 .
8. The method of claim 6 , wherein growing the microorganism is performed in the presence of exogenous gamma-hydroxybutyrate (GHB), exogenous α-ketoglutarate, or exogenous succinate.
9. The method of claim 6 , further comprising recovering the 1,4-butanediol.
10. The method of claim 6 , wherein the multicarbon product is 1,4-butanediol.
11. The method of claim 6 , further comprising contacting the 1,4-BDO with a catalyst.
12. The method of claim 11 , wherein tetrahydrofuran (THF) is formed after 1,4-butanediol is contacted with the catalyst.
13. The method of claim 6 , further comprising contacting the 1,4-BDO with a dicarboxylic acid/anhydride.
14. The method of claim 13 , wherein a polyurethane is formed after the 1,4-butanediol is contacted with the dicarboxylic acid/anhydride.
15. The method of claim 11 , further comprising transesterifying the 1,4-butanediol.
16. The method of claim 15 , wherein polybutylene terephthalate (PBT) is formed after the 1,4-butanediol is transesterified.