Production of quinone derived compounds in oleaginous yeast and fungi
The present invention provides systems for producing engineered oleaginous yeast or fungi that express quinone derived compounds.
1. An engineered Y. lipolytica strain comprising:
a combination of two or more quinonogenic modifications selected from the group consisting of:
a. increased expression or activity of a GGPP synthase polypeptide;
b. increased expression or activity of a truncated HMG CoA reductase polypeptide;
c. increased expression or activity of a 4-hydroxybenzoate polyprenyl transferase polypeptide;
d. increased expression or activity of a decaprenyl diphosphate synthase polypeptide;
e. increased expression or activity of a DAHP synthase polypeptide;
f. increased expression or activity of a chorismate lyase polypeptide;
g. increased expression or activity of a shikimate pathway polypeptide;
h. increased expression or activity of a chorismate mutase polypeptide;
i. increased expression or activity of a transketolase polypeptide;
j. increased expression or activity of an FPP synthase polypeptide;
k. increased expression or activity of an IPP isomerase polypeptide;
l. increased expression or activity of an HMG-CoA synthase polypeptide;
m. increased expression or activity of a mevalonate kinase polypeptide;
n. increased expression or activity of a phosphomevalonate kinase polypeptide;
o. increased expression or activity of a mevalonate pyrophosphate decarboxylate polypeptide;
p. increased expression or activity of a cytosolic malic enzyme polypeptide;
q. increased expression or activity of a malate dehydrogenase polypeptide;
r. increased expression or activity of an AMP deaminase polypeptide;
s. increased expression or activity of a glucose 6 phosphate dehydrogenase polypeptide;
t. increased expression or activity of a malate dehydrogenase homolog2 polypeptide;
v. increased expression or activity of a GND1-6-phosphogluconate dehydrogenase polypeptide;
w. increased expression or activity of a isocitrate dehydrogenase polypeptide;
x increased expression or activity of a IDH2-isocitrate dehydrogenase polypeptide;
y. increased expression or activity of a fructose 1,6 bisphosphatase polypeptide;
z. increased expression or activity of an Erg10-acetoacetyl CoA thiolase polypeptide;
aa. increased expression or activity of an ATP citrate lyase subunit 2 polypeptide;
bb. increased expression or activity of an ATP citrate lyase subunit 1 polypeptide;
cc. increased expression or activity of a chorsimate synthase polypeptide;
dd. decreased expression or activity of a squalene synthase polypeptide;
ee. decreased expression or activity of a prenyldiphosphate synthase polypeptide; and
ff. decreased expression or activity of a PHB polyprenyltransferase polypeptide;
wherein as a result of the combination of two or more quinonogenic modifications the engineered Y. lipolytica strain produces at least one quinone derived compound to at least about 1% of its dry cell weight; and
wherein the engineered strain can accumulate lipid to at least about 20% of its dry cell weight.
2. The engineered Y. lipolytica strain of claim 1 , wherein the combination of two or more quinonogenic modifications comprises:
a. increased expression or activity of a GGPP synthase polypeptide;
b. increased expression or activity of a 4-hydroxybenzoate polyprenyl transferase polypeptide;
c. increased expression or activity of a decaprenyl diphosphate synthase polypeptide;
d. increased expression or activity of a DAHP synthase polypeptide; and
e. increased expression or activity of a chorismate lyase polypeptide.
3. The engineered Y. lipolytica strain of claim 1 , further comprising at least one oleaginic modification.