title: Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering.
abstract: Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases' many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field.
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA. mburkart@ucsd.edu.
authors.forename: Joris
authors.initials: J
authors.lastname: Beld
authors.forename: D John
authors.initials: DJ
authors.lastname: Lee
authors.forename: Michael D
authors.initials: MD
authors.lastname: Burkart
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D051080:Acyl-Carrier Protein S-Malonyltransferase / Q000737:chemistry / Q000378:metabolism; D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism; D053898:Biosynthetic Pathways; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000737:chemistry / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000737:chemistry / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000378:metabolism
chemical_list: D000213:Acyl Carrier Protein; D005227:Fatty Acids; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D000217:Acyltransferases; D051080:Acyl-Carrier Protein S-Malonyltransferase; D064429:Fatty Acid Synthases; D013869:Thiolester Hydrolases; D006836:Hydro-Lyases