Fatty acid productivity
AssigneeWilliam Marsh Rice University
InventorsKa-Yiu SUN, Wei LI
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Abstract
The present disclosure relates to an engineered microbe capable of improved productivity of fatty acid or fatty acid derivative. An NAD+-dependent 3-oxoacyl-ACP reductase or NAD+-dependent 3-oxoacyl-CoA reductase replaces or supplements the native NADP+-dependent 3-oxoacyl-ACP reductase so as to utilize the higher availability of NAD+ rather than NADP+ in the cell. Higher production, yield and titer of fatty acids are therefore obtained. Such microbes can be combined with other mutations to further improve yield of fatty acids or fatty acid derivatives.
Claims21
An engineered microbe with improved productivity of a fatty acid or fatty acid derivative, said microbe comprising type II fatty acid synthesis enzymes (FASII) and:
- a) an overexpressed NAD+-dependent 3-oxoacyl-ACP reductase or an overexpressed NAD+-dependent 3-oxoacyl-CoA reductase that replaces or supplements a native NADP+-dependent 3-oxoacyl-ACP reductase or 3-oxoacyl-CoA reductase (respectively);
- and one or more overexpressed acyl-ACP thioesterases (TE).
A genetically engineered microbe, said microbe being a FASII bacteria comprising an exogenous overexpressed NAD+-dependent 3-oxoacyl-ACP reductase and one or more overexpressed acyl-ACP thioesterase (TE), wherein said bacteria makes more fatty acid than a comparable bacteria with only a native NADP+-dependent 3-oxoacyl-ACP reductase and said one or more overexpressed TE.
A genetically engineered microbe, said microbe being an Escherichia comprising an exogenous overexpressed NAD+-dependent 3-oxoacyl-ACP reductase and one or more overexpressed acyl-ACP thioesterases (TE), wherein said Escherichia makes more fatty acid than a comparable Escherichia with only a native NADP+-dependent 3-oxoacyl-ACP reductase.
An FASII microbe genetically engineered for improved fatty acid production, said FASII microbe comprising a native NADP+-dependent 3-oxoacyl-ACP reductase gene replaced or supplemented with an overexpressed exogenous NAD+-dependent 3-oxoacyl-ACP reductase gene, plus one or more overexpressed TE enzymes, wherein said FASII microbe makes more fatty acid than a comparable FASII microbe with only said native NADP+-dependent 3-oxoacyl-ACP reductase and said one or more overexpressed TE enzymes, said microbe further comprising reduced activity of one or enzymes selected from beta-oxidation cycle enzymes, acetate synthesis enzymes, lactate synthesis enzymes, formate synthesis enzymes, ethanol synthesis enzymes, glycolytic enzymes or tricarboxylic acid (TCA) cycle enzymes.
Dependencies are inferred from the claim text.