AbstractWith the aid of the (R)‐ and (S)‐configurated malonates (IV) it is shown that in the enzymatic formation of orsellinic acid (III) from malonate (I) the proton abstraction at the positions 3 and 5 of the polyketide precursor (II) is not stereospecific and therefore not enzyme‐mediated; it also may occur while the molecule still resides in the chiral protein environment.