title: Engineering synthetic recursive pathways to generate non-natural small molecules.
abstract: Recursive pathways are broadly defined as those that catalyze a series of reactions such that the key, bond-forming functional group of the substrate is always regenerated in each cycle, allowing for a new cycle of reactions to begin. Recursive carbon-chain elongation pathways in nature produce fatty acids, polyketides, isoprenoids and α-keto acids (αKAs), which all use modular or iterative approaches for chain elongation. Recently, an artificial pathway for αKA elongation has been built that uses an engineered isopropylmalate synthase to recursively condense acetyl-CoA with αKAs. This synthetic approach expands the possibilities for recursive pathways beyond the modular or iterative synthesis of natural products and serves as a case study for understanding the challenges of building recursive pathways from nonrecursive enzymes. There exists the potential to design synthetic recursive pathways far beyond what nature has evolved.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, California, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Felnagle
authors.forename: Asha
authors.initials: A
authors.lastname: Chaubey
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Noey
authors.forename: Kendall N
authors.initials: KN
authors.lastname: Houk
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
mesh_terms: D015079:2-Isopropylmalate Synthase / Q000737:chemistry* / Q000235:genetics; D000105:Acetyl Coenzyme A / Q000737:chemistry*; D001665:Binding Sites; D057486:Carbon Cycle; D002384:Catalysis; D007651:Keto Acids / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D015202:Protein Engineering / Q000379:methods; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D013379:Substrate Specificity; D058615:Synthetic Biology / Q000379:methods
chemical_list: D007651:Keto Acids; D054852:Small Molecule Libraries; D000105:Acetyl Coenzyme A; D015079:2-Isopropylmalate Synthase