Publications

• Biocatalytic strategies towards [4+2] cycloadditions.

  Lichman B.R., O'Connor S.E., Kries H.

  Long sought after [4+2] cyclases have sprouted up in numerous biosynthetic pathways in recent years, raising hopes for biocatalytic solutions to cycloaddition catalysis, an important problem in chemical synthesis. In a few cases, detailed pictures of the inner workings of these catalysts have emer ... >> More

  Long sought after [4+2] cyclases have sprouted up in numerous biosynthetic pathways in recent years, raising hopes for biocatalytic solutions to cycloaddition catalysis, an important problem in chemical synthesis. In a few cases, detailed pictures of the inner workings of these catalysts have emerged, but intense efforts to gain deeper understanding are underway by means of crystallography and computational modelling. This Minireview aims to shed light on the catalytic strategies that this highly diverse family of enzymes employs to accelerate and direct the course of [4+2] cycloadditions with reference to small-molecule catalysts and designer enzymes. These catalytic strategies include oxidative or reductive triggers and lid-like movements of enzyme domains. A precise understanding of natural cycloaddition catalysts will be instrumental for customizing them for various synthetic applications. << Less

  Chemistry 25:6864-6877(2019) [PubMed] [EuropePMC]

  This publication is cited by 6 other entries.

• Inverted stereocontrol of iridoid synthase in snapdragon.

  Kries H., Kellner F., Kamileen M.O., O'Connor S.E.

  The natural product class of iridoids, found in various species of flowering plants, harbors astonishing chemical complexity. The discovery of iridoid biosynthetic genes in the medicinal plant <i>Catharanthus roseus</i> has provided insight into the biosynthetic origins of this class of natural pr ... >> More

  The natural product class of iridoids, found in various species of flowering plants, harbors astonishing chemical complexity. The discovery of iridoid biosynthetic genes in the medicinal plant <i>Catharanthus roseus</i> has provided insight into the biosynthetic origins of this class of natural product. However, not all iridoids share the exact five-to six-bicyclic ring scaffold of the <i>Catharanthus</i> iridoids. For instance, iridoids in the ornamental flower snapdragon (<i>Antirrhinum majus</i>, Plantaginaceae family) are derived from the C7 epimer of this scaffold. Here we have cloned and characterized the iridoid synthase enzyme from <i>A. majus</i> (AmISY), the enzyme that is responsible for converting 8-oxogeranial into the bicyclic iridoid scaffold in a two-step reduction-cyclization sequence. Chiral analysis of the reaction products reveals that AmISY reduces C7 to generate the opposite stereoconfiguration in comparison with the <i>Catharanthus</i> homologue CrISY. The catalytic activity of AmISY thus explains the biosynthesis of 7-epi-iridoids in <i>Antirrhinum</i> and related genera. However, although the stereoselectivity of the reduction step catalyzed by AmISY is clear, in both AmISY and CrISY, the cyclization step produces a diastereomeric mixture. Although the reduction of 8-oxogeranial is clearly enzymatically catalyzed, the cyclization step appears to be subject to less stringent enzyme control. << Less

  J. Biol. Chem. 292:14659-14667(2017) [PubMed] [EuropePMC]