title: Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase.
abstract: 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.
authors: Department of Chemical Engineering and Materials Science, University of California, Irvine, CA, 92697-2575 USA.
authors: Jin Wook
authors: JW
authors: Choi
authors: Department of Chemical Engineering and Materials Science, University of California, Irvine, CA, 92697-2575 USA. Electronic address: ndasilva@uci.edu.
authors: Nancy A
authors: NA
authors: Da Silva
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D061065:Polyketides / Q000032:analysis / Q000378:metabolism*; D015202:Protein Engineering; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012459:Salicylates; D016415:Sequence Alignment
chemical_list: D005227:Fatty Acids; D061065:Polyketides; D029701:Saccharomyces cerevisiae Proteins; D012459:Salicylates; D000103:Acetyl-CoA Carboxylase; C033069:methyl salicylate
keywords: 6-MSA; Acc1; Fatty acids; Phosphorylation; Polyketides; Saccharomyces cerevisiae