Recently, we have adapted the idea of Zhang and Kyler of using adipate as a
prosthetic group, but in contrast to these authors (whose aim was to conduct n-6
lipoxygenation), our goal was to realize a 5-lipoxygenation on the carbon skeleton
of AA by using SBLOX-1. Such a 5-lipoxygenation would result from an inverse
orientation of the substrate in the active site of the enzyme (Figure 11).
The reverse orientation of AA is clearly disfavored (Figure 11), since both pockets
will be filled with a residue of opposite nature. To favor such an inverse orientation,
the carboxylic function should be transformed to a more polar one (methyl ester for
348 16 Properties and Applications of Lipoxygenases
Figure 10. Action of SBLOX-1 on various unnatural substrates constructed from methylene interrup-
ted dienic (Z,Z) alcohols and adipic acid (Zhang and Kyler, 1989).
Figure 11. Regiospecificity of SBLOX-1 according to the orientation of the substrate in the active site
(Martini et al., 1996a).