The insertion or extrusion of small molecular fragments or atoms from existing carbo-or heterocyclic scaffolds has for a long time been a logical consideration to address challenging ring structures in synthetic-organic chemistry. These ring contraction and ring expansion reactions offer the great advantage over for example cyclizations in that they do not pose stringent limitation regarding ring sizes. Furthermore, the contraction/extension approach allows for the easy conversion of readily available or abundant cyclic precursors to yield more complex, value-added products. Traditional ring contraction reactions often proceed through the migration of bonds to electron-deficient intermediates, including Wagner-Meerwein, (semi)pinacol, and Wolff rearrangements, or through skeletal realignment of anionic intermediates such as in Favorskii, and benzilic acid rearrangements. Other types of ring contractions operate through extrusion of small molecules as exemplified in Ramberg-Bäcklund olefinations (loss of SO2), the decomposition of diazenes (loss of N2), or photochemical decarbonylations (loss of CO). But ring contraction reactions are not entirely limited to the synthetic chemistry world and also Nature does occasionally take advantage of similar transformations in the biosynthesis of complex metabolites. Examples of these natural ring contractions include the biosynthesis of rare sugars such as the rearrangement of activated pyranoses to UDP-D-apiose, the generation of the corrin core of vitamin B12 through the natural contractase CbiH60, the conversion of a benzodiazepinedione to the quinolone alkaloid viridicatin, or the xanthone contractions to cyclopentadienols such as coniothyrione, and the remisporines. On the other hand, synthetic biotransformations addressing ring contractions in vitro have so far remained scarce at best. While our recent research has focussed to a significant extent on the (stereo)selective and biocatalytic synthesis of five-membered oxygen heterocycles, the herein described methodology exploiting an enzymatic ring contraction for the production of g-butenolides has developed purely serendipitously and as a result of an unanticipated and undesired side reaction. Even though certain similarities to the UDP-D-apiose biosynthesis (via UAXS) deciphered by Mattevi and Nidetzky are apparent (Scheme 1a) -specifically the redox self-sufficient nature of the UAXS applying a nicotinamide cofactor to mediate a natural borrowing hydrogen catalysis cyclethe focus of the title reaction is on synthetic utility to deliver g-lactone building blocks in high optical purity. This unprecedented biocatalytic synthesis tool based on readily available dehydrogenases exploits a much more rare inverse borrowing hydrogen strategy in which the reduced cofactor acts as H-donor and the substrate undergoes a reduction-oxidation sequence (Scheme 1b). The study covers a detailed account on the underlying pyranone chemistry, an in-depth discussion on substrate scope and limitations as well as the incorporation of the new contractase module into a complex multi-enzyme in vitro cascade.