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US 10,851,393 B2Granted
KAS-III free FA synthesis
AssigneeWilliam Marsh Rice University
InventorsKa-Yiu San, Xian Zhang, Hui Wu, Dan Wang
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AssigneeWilliam Marsh Rice University
InventorsKa-Yiu San, Xian Zhang, Hui Wu, Dan Wang
Estimating the term…
The present disclosure describes a genetically engineered a KASIII-independent fatty acid biosynthetic pathway that makes use of the promiscuous nature of the rest of the FAS enzymes (3-ketoacyl-ACP synthetase, 3-ketoacyl-ACP reductase, 3-hydroxyacyl ACP dehydrase, enoyl-ACP reductase) to bypass the KASIII step by providing a Co-A precursor of two or higher than two carbons (such as the four carbon butyryl-CoA) as the starting molecule. Since many CoA-based starter molecules can be supplied for the fatty acid synthesis, much more diversified products can be obtained with various carbon-chain lengths. As such, this disclosure will serve as a powerful and efficient platform to produce low to medium chain length products carrying many different functional groups.
A genetically engineered microbe comprising:
A genetically engineered microbe having a β-ketoacyl-acyl carrier protein synthase III (KASIII) independent fatty acid synthesis (FAS) pathway that makes a product from a starter molecule of >2 carbons or >3 carbons, said starter molecule excluding acetyl-CoA or propionyl-coA, using FAS enzymes (except for KASIII), said microbe having reduced KASIII activity, an overexpressed acyl ACP thioesterase (TE), and reduced native acyl-carrier protein (ACP) dependent fatty acid biosynthesis, malonyl-CoA-ACP transacylase, and acetyl-CoA carboxylase.
A recombinant bacteria comprising KASIII− (β-ketoacyl-acyl carrier protein synthase III−), TE+ (thioesterase+), PhaA+ (beta-ketothiolase+), PhaB+ (acetoacetyl-CoA reductase+), TER+ (trans-enoyl-CoA reductase+), and either FabZ+ (3-hydroxyacyl-[acyl-carrier-protein] dehydratase+) or crt+ (crotonase+).
Dependencies are inferred from the claim text.