Enzymatic Upgrading of Biomass-Derived Aldoses to Rare Deoxy Ketoses Catalyzed by Transketolase Variants

ChemSusChem. 2024 Dec 4:e202401834. doi: 10.1002/cssc.202401834. Online ahead of print.

Abstract

A sustainable, convenient, scalable, one-step method for the two-carbon chain elongation of cheap and biomass-derived pentoses (l-arabinose, and 2-deoxy-d-ribose) and hexose l-rhamnose was developed to produce Cn+2 deoxy ketoses (C-7 and C-8) using transketolase, an enzyme catalyzing the quasi-irreversible transfer of a ketol group from an α-keto acid to an aldehyde. Deoxygenated ketoses - commonly obtained by chemical synthesis - were afforded through a suitable combination of both nucleophile and electrophile substrates in the presence of rationally designed TK variants. Pyruvate as nucleophile with pentose l-arabinose (C-5) as electrophile gave 1-deoxy-L-gluco-heptulose (C-7), while ß-hydroxypyruvate (HPA) as nucleophile with acceptors 2-deoxy-d-ribose (C-5) and 6-deoxy-l-mannose (l-rhamnose) (C-6) led to formation of 4-deoxy-d-altro-heptulose (C-7) and 8-deoxy-l-glycero-l-galacto-octulose (C-8), respectively. These three deoxy ketoses were easily obtained with efficient TK variants under mild conditions with complete or high substrate conversions, good to excellent yields and high diastereoselectivities. This strategy offers interesting prospects to study the biological activities of these three rare and valuable deoxy ketoses on various cellular targets.

Keywords: Biocatalysis* C-C bond formation* enzyme engineering; bio-derived aldoses* deoxy ketoses.