Carrier protein structure and recognition in polyketide and nonribosomal peptide biosynthesis.
Carrier proteins, 80-100 residues in length, serve as information-rich platforms to present growing acyl and peptidyl chains as covalently tethered phosphopantetheinyl-thioester intermediates during the biosynthesis of fatty acid, polyketide, and nonribosomal natural products. Carrier proteins are recognized both in cis and in trans by partner catalytic domains that effect chain-elongating condensations, redox adjustments, other tailoring steps, and finally kinetically controlled disconnection and release of the mature natural product. Dissection of regions of carrier proteins that are specifically recognized by upstream and downstream catalytic partner proteins is deciphering the logic for multiprotein assembly line construction of these large classes of natural products.
Lai
Jonathan R
JR
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Koglin
Alexander
A
Walsh
Christopher T
CT
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism*; D046908:Peptide Biosynthesis, Nucleic Acid-Independent / Q000502:physiology*; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D002352:Carrier Proteins; D018942:Macrolides; D010455:Peptides; D048630:Polyketide Synthases; D010453:Peptide Synthases