Recognition of (2S)-aminomalonyl-acyl carrier protein (ACP) and (2R)-hydroxymalonyl-ACP by acyltransferases in zwittermicin A biosynthesis.
Polyketide synthases elongate a polyketide backbone by condensing carboxylic acid precursors that are thioesterified to either coenzyme A or an acyl carrier protein (ACP). Two of the three known ACP-linked extender units, (2S)-aminomalonyl-ACP and (2R)-hydroxymalonyl-ACP, are found in the biosynthesis of the agriculturally important antibiotic zwittermicin A. We previously reconstituted the formation of (2S)-aminomalonyl-ACP and (2R)-hydroxymalonyl-ACP from the primary metabolites l-serine and 1,3-bisphospho-d-glycerate. In this report, we characterize the two acyltransferases involved in the specific transfer of the (2S)-aminomalonyl and (2R)-hydroxymalonyl moieties from the ACPs associated with extender unit formation to the ACPs integrated into the polyketide synthase. This work establishes which acyltransferase recognizes each extender unit and also provides insight into the substrate selectivity of these enzymes. These are important step toward harnessing these rare polyketide synthase extender units for combinatorial biosynthesis.
Chan
Yolande A
YA
Department of Bacteriology, University of Wisconsin, 1550 Linden Drive, Madison, Wisconsin 53706, USA.
Thomas
Michael G
MG
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000217:Acyltransferases / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008314:Malonates / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010957:Plasmids; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013646:Tartronates / Q000378:metabolism*
D000213:Acyl Carrier Protein; D008314:Malonates; D010455:Peptides; D013646:Tartronates; C019249:aminomalonic acid; C088290:zwittermicin A; C032973:tartronic acid; D000217:Acyltransferases