In our quest to discover new synthetic applications that make use of readily available, commercial enzyme formulations, we recently reported on an isomerization system, where alcohol dehydrogenases convert easy-to-obtain racemic Achmatowicz pyranones to the corresponding optically pure d-lactones in an enantioconvergent and redox-self-sufficient manner. Taking inspiration from an iridium-catalyzed protocol, , this biocatalytic interpretation of the classical borrowing hydrogen catalysis opens new opportunities for the utilization of enzymes (Scheme 2a). Nevertheless, the study did not clearly answer mechanistic details (Scheme 2b), such as whether the overall redox-neutral process would proceed through a ketolactone intermediate (3a) via oxidation of the pyranone as suggested for the iridium catalysis, or through initial reduction and formation of a transient hydroxylactol (4a). While the former route resembles the typical borrowing hydrogen steps where the catalyst temporarily removes H2 equivalents from the substrate and stores them as transition metal hydride species (or a reduced enzyme cofactor), the latter one would constituted an inverse borrowing hydrogen pathway with NAD(P)H being the borrowing entity. Surprisingly, when trying to incorporate the enzymatic methodology into an in vivo tool by co-expressing the necessary proteins in a bacterial host, some cellular factories -particularly in a more reductive environment -delivered five-membered aromatic furan products as main metabolites (Scheme 2c). As 1a is usually obtained through oxidation of furfuryl alcohol 5a in an Achmatowicz oxidation, 54-57 a retro-Achmatowicz pathway was proposed in which, under strongly reducing conditions, the pyranone substrates are suffering an undesired ring contraction. Biosynthetic studies on the origin of furan metabolites have deciphered pathways where either oxidative or hydrolytic steps provide five-membered hemiacetals that apparently undergo spontaneous dehydration to the aromatic heterocycles (Scheme 2d). In line with this natural precedence, it seemed likely that a reduction-induced isomerization may in fact deliver a furanose intermediate that would dehydrate to the undesired aromatic side product (Scheme 2e). Even if such a retro-Achmatowicz scenario might be of certain academic interest and can in fact be an interesting tools in a cascade reaction setting, the synthetic value of this particular kind of defunctionalization would be at least questionable. On the other hand, we speculated that interception of the intermediates arising from the proposed pyranose-furanose isomerization would allow us to deviate the biocatalytic pathway and turn the undesired ring contraction to a novel and synthetically more appealing heterocyclic methodology. In our design, we imagined that interruption of the retro-Achmatowicz transformation by dehydrogenation of the five-membered hemiacetal would enable us to produce gamma-lactones in a stereoselective fashion (Scheme 2f). In this overall redox-self-sufficient process -i.e. without the need of any sacrificial reductants or oxidants -biomass-derived Achmatowicz pyranones could be directly converted to synthetically highly valuable g-butenolides. As the reaction would be induced by a dehydrogenase-catalyzed reduction, the racemic, configurationally labile starting materials could be converted to optically enriched products in an enantioconvergent fashion. In order to redirect the original protocol, the catalyst discovery has to focus on a few key aspects. In the first step of the catalysis, high enantioselectivity has to be paired with the inability to oxidize the six-membered hydroxylactol 3 further to the dlactone (2). While a similar effect could be achieved by modulation of the redox environment (i.e. in a stepwise reduction-oxidation scenario), enzymes with the intrinsic deficiency or even better with a certain preference for five-membered furanoses (6) may allow for a true one-pot cascade catalysis. These qualities could of course also be combined in an enzyme-pair with designated redox tasks. Lastly, the reaction conditions themselves (or rapid oxidation of 6 to yield 7) would need to disfavour the undesired dehydration to the competing furans (5).