Cover Feature: Characterization of ActVI‐ORF3 and ActVI‐ORF4 as Lactonizing and Delactonizing Enzymes in Relation to Metabolic Flux in Actinorhodin Biosynthesis (ChemBioChem 9/2025)

The front cover shows the biosynthetic pathway of actinorhodin (ACT), a tricyclic dimer polyketide. ACT is biosynthesized from malonyl-CoA units by multiple enzymes (blue arrow) via monomeric DHK-OH. Intracellular ACT and DHK-OH are converted into their lactone-forms (yellow arrow) diffusible outside the cell. ActVI-ORF4 can reducibly delactonize KAL-OH to DHK-OH (green arrow), but not γ-ACT. Therefore, these two enzymes could appear to efficiently regulate metabolic flux in ACT biosynthesis. More details can be found in article 10.1002/cbic.202500049 by Makoto Hashimoto, Koji Ichinose, and co-workers.