Fig. 1: Schematic representations of the different pathways to produce irone.
From: Total enzymatic synthesis of cis-α-irone from a simple carbon source
The chemical route uses acid to catalyse cyclization of methyl-3-psi-ionone, which is not a known natural product. Chemical synthesis produces a racemic mixture containing (1 R, 5 R)-trans-α-irone (1R5R), (1 S, 5 S)-trans-α-irone (1 S5S), (1S, 5 R)-cis-α-irone (1S5R), (1 R, 5 S)-cis-α-irone (1R5S), (5 R)-β-irone and (5 S)-β-irone. The native biosynthesis route was proposed based on a radiolabelling study9, and a bifunctional methyltransferase and cyclase (bMTC) was hypothesized to convert iridal directly to cycloiridal. Cycloiridal is asymmetric, so only one molecule of α-irone is produced from the C30 precursor. The resulting carbon yield is 46.7%. The artificial biosynthesis route was designed by combining both the chemical and biological synthesis knowledge, namely, to use a promiscuous bMTC to convert psi-ionone into α-irone. Two molecules of psi-ionone molecules are readily formed from the symmetric C40 lycopene; hence, two molecules of α-irone are expected to be formed from the C40 precursor. The resulting carbon yield is 65%, which is higher than the native biosynthesis route. The abbreviations are as follows. SAM: S- adenosylmethionine. SAH, S-adenosylhomocysteine; CCD1, carotenoid cleavage dioxygenase 1.
