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Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase

Paper ID Volume ID Publish Year Pages File Format Full-Text
23031 43413 2014 4 PDF Available
Title
Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase
Abstract

•Identified Acc1 mutant (S1157A) insensitive to deactivation via phosphorylation.•Activity of Acc1S1157A was 9-fold higher following glucose depletion relative to WT.•The mutant Acc1 led to 3-fold increases in both polyketide and fatty acid production.

Polyketides and fatty acids are important in the production of pharmaceuticals, industrial chemicals, and biofuels. The synthesis of the malonyl-CoA building block, catalyzed by acetyl-CoA carboxylase (Acc1), is considered a limiting step to achieving high titers of polyketides and fatty acids in Saccharomyces cerevisiae. Acc1 is deactivated by AMP-activated serine/threonine protein kinase (Snf1) when glucose is depleted. To prevent this deactivation, the enzyme was aligned with the Rattus norvegicus (rat) Acc1 to identify a critical amino acid (Ser-1157) for phosphorylation and deactivation. Introduction of a S1157A mutation into Acc1 resulted in 9-fold higher specific activity following glucose depletion. The enzyme was tested in yeast engineered to produce the polyketide 6-methylsalisylic acid (6-MSA). Both 6-MSA and native fatty acid levels increased by 3-fold. Utilization of this modified Acc1 enzyme will also be beneficial for other products built from malonyl-CoA.

Keywords
Saccharomyces cerevisiae; Acc1; Phosphorylation; 6-MSA; Polyketides; Fatty acids
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Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 187, 10 October 2014, Pages 56–59
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
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Online Support
Any Questions? feel free to contact us