Enantioselective Reductive Oligomerization of Carbon Dioxide into l-Erythrulose via a Chemoenzymatic Catalysis

A cell-free enantioselective transformation of the carbon atom of CO2 has never been reported. In the urgent context of transforming CO2 into products of high value, the enantiocontrolled synthesis of chiral compounds from CO2 would be highly desirable. Using an original hybrid chemoenzymatic catalytic process, we report herein the reductive oligomerization of CO2 into C3 (dihydroxyacetone, DHA) and C4 (l-erythrulose) carbohydrates, with perfect enantioselectivity of the latter chiral product. This was achieved with the key intermediacy of formaldehyde. CO2 is first reduced selectively by 4e– by an iron-catalyzed hydroboration reaction, leading to the isolation and complete characterization of a new bis(boryl)acetal compound derived from dimesitylborane. In an aqueous buffer solution at 30 °C, this compound readily releases formaldehyde, which is then involved in selective enzymatic transformations, giving rise either (i) to DHA using a formolase (FLS) catalysis or (ii) to l-erythrulose with a cascade reaction combining FLS and d-fructose-6-phosphate aldolase (FSA) A129S variant. Finally, the nature of the synthesized products is noteworthy, since carbohydrates are of high interest for the chemical and pharmaceutical industries. The present results prove that the cell-free de novo synthesis of carbohydrates from CO2 as a sustainable carbon source is a possible alternative pathway in addition to the intensely studied biomass extraction and de novo syntheses from fossil resources.We wish to thank the reviewers, whose comments helped to improve the manuscript and in particular the 1H NMR interpretation of compound 3-13C. S.D. thanks Région Midi-Pyrénées and Université Fédérale de Toulouse for a doctoral fellowship. S.B. thanks the ANR programme JCJC “ICC”. C. Bijani is gratefully acknowledged for his help in the simulation of 3-13C. K.G.-S., C.D., and R.F. thank the Carnot 3BCAR (project SUCRES), including the fellowship of K.G.-S. R.F. thanks the Mission for Transversal and Interdisciplinary Initiatives of the CNRS (project CASCADE). We gratefully thank N. Monties, S. Pizzut, and M. Guicherd for technical assistance in HPLC experiments, G. Cioci for assistance in DSF experiments and protein purification, and the ICEO facility dedicated to enzyme screening and discovery, part of the Integrated Screening Platform of Toulouse (PICT, IBiSA). DSF is part of the Integrated Screening Platform of Toulouse (PICT, IBiSA). We thank S. Heux and A. De Simone for the generous gift of a plasmid containing the gene encoding for FLS. J. Durand is gratefully acknowledged for his help in isolating compound 4-13C by semipreparative HPLC. P.C. thanks the Ministerio de Ciencia e Innovación (MICIN), the Fondo Europeo de Desarrollo Regional (FEDER) (grant RTI2018-094637-B-I00), and Programación Conjunta Internacional (PCI2018-092937), through the initiative ERA CoBioTechPeer reviewe