Production of isoprenoids

摘要

A recombinant yeast that makes an isoprenoid compound is provided. The yeast comprises an endogenous mevalonate pathway comprising (i) an enzyme that converts acetyl-CoA to acetoacetyl-CoA, (ii) an enzyme that converts acetoacetyl-CoA to hydroxymethylglutaryl-CoA, (iii) an enzyme that converts hydroxymethylglutaryl-CoA to mevalonic acid, (iv) an enzyme that converts mevalonic acid to phosphomevalonic acid, (v) an enzyme that converts phosphomevalonic acid to phosphomevalonate, and (vi) an enzyme that converts phosphomevalonate to isopentenyl pyrophosphate. The yeast further comprises heterologous nucleic acid sequences encoding an enzyme that converts hydroxymethylglutaryl-CoA to mevalonic acid, an enzyme that converts mevalonic acid to phosphomevalonic acid, an enzyme that converts phosphomevalonic acid to phosphomevalonate, and an enzyme that converts phosphomevalonate to isopentenyl pyrophosphate. Carbon flow through the mevalonate pathway is increased in the recombinant yeast compared to a yeast that does not comprise the heterologous nucleic acid molecule encoding an enzyme that converts hydroxymethylglutaryl-CoA to mevalonic acid.

主权项

1. A recombinant yeast that is capable of making an isoprenoid compound, the recombinant yeast comprising:
an endogenous mevalonate pathway comprising (i) an enzyme that converts acetyl-CoA to acetoacetyl-CoA, (ii) an enzyme that converts acetoacetyl-CoA to hydroxymethylglutaryl-CoA, (iii) an enzyme that converts hydroxymethylglutaryl-CoA to mevalonic acid, (iv) an enzyme that converts mevalonic acid to phosphomevalonic acid, (v) an enzyme that converts phosphomevalonic acid to phosphomevalonate, and (vi) an enzyme that converts phosphomevalonate to isopentenyl pyrophosphate; and at least one heterologous nucleic acid sequence encoding an enzyme that converts hydroxymethylglutaryl-CoA to mevalonic acid; at least one heterologous nucleic acid sequence encoding an enzyme that converts mevalonic acid to phosphomevalonic acid; at least one heterologous nucleic acid sequence encoding an enzyme that converts phosphomevalonic acid to phosphomevalonate; and at least one heterologous nucleic acid sequence encoding an enzyme that converts phosphomevalonate to isopentenyl pyrophosphate; wherein carbon flow through the mevalonate pathway from mevalonate to isopentenyl pyrophosphate is increased in the recombinant yeast compared to a yeast that does not comprise the at least one heterologous nucleic acid sequence encoding the enzyme that converts mevalonic acid to phosphomevalonic acid, the at least one heterologous nucleic acid sequence encoding the enzyme that converts phosphomevalonic acid to phosphomevalonate, and the at least one heterologous nucleic acid sequence encoding the enzyme that converts phosphomevalonate to isopentenyl pyrophosphate.