Structure and mechanism of assembly line polyketide synthases.
Assembly line polyketide synthases (PKSs) are remarkable biosynthetic machines with considerable potential for structure-based engineering. Several types of protein-protein interactions, both within and between PKS modules, play important roles in the catalytic cycle of a multimodular PKS. Additionally, vectorial biosynthesis is enabled by the energetic coupling of polyketide chain elongation to the channeling of intermediates between successive modules. A combination of high-resolution analysis of smaller PKS components and lower resolution characterization of intact modules and bimodules has yielded insights into the structure and organization of a prototypical assembly line PKS. This review discusses our understanding of key structure-function relationships in this family of megasynthases, along with a recap of key unanswered questions in the field.
Department of Chemistry, Stanford University, Stanford, CA 94305, United States.
Thomas
T
Robbins
Department of Chemistry, Stanford University, Stanford, CA 94305, United States.
Yu-Chen
YC
Liu
Department of Chemistry, Brown University, Providence, RI 02912-9108, United States.
David E
DE
Cane
Department of Chemistry, Stanford University, Stanford, CA 94305, United States; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, United States. Electronic address: khosla@stanford.edu.
Chaitan
C
Khosla
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
D000213:Acyl Carrier Protein; D048630:Polyketide Synthases