Stereospecific manipulation of hydrogen atoms with opposite absolute orientations during the biosynthesis of the polyketide 6-methylsalicylic acid from chiral malonates in Penicillium patulum

Abstract

(R)- and (S)-[1-¹³C; 2-²H]malonate have been synthesized chemically and transformed, using succinyl-CoA transferase, into their respective paired malonyl-CoA derivatives; incorporation into 6-methylsalicylic acid has been achieved using homogeneous 6-methylsalicylic acid synthase isolated from Penicillium patulum; mass spectra of the resulting 6-methylsalicylic acids revealed that the hydrogen atoms removed from the two methylene groups at the 2- and 4-positions in the putative polyketide intermediate, have opposite absolute stereochemistry.