Opine dehydrogenases, an underexplored enzyme family for the enzymatic synthesis of chiral amines

Abstract

Opines and opine‐type chemicals are valuable natural products with diverse biochemical roles, and potential synthetic building blocks of bioactive compounds. Their synthesis involves reductive amination of ketoacids with amino acids. This transformation has high synthetic potential in producing enantiopure secondary amines. Nature has evolved opine dehydrogenases for this chemistry. To date, only one enzyme has been used as biocatalyst, however, analysis of the available sequence space suggests more enzymes to be exploited in synthetic organic chemistry. This review summarizes the current knowledge of this underexplored enzyme class, highlights key molecular, structural, and catalytic features with the aim to provide a comprehensive general description of opine dehydrogenases, thereby supporting future enzyme discovery and protein engineering studies.

Discovery and biocatalytic characterization of opine dehydrogenases by metagenome mining

“…The newly discovered opine dehydrogenases have a clear preference for l -amino acids in line with previous observations (Telek et al 2023 ). The diastereoselectivity (dictated by the stereoselectivity in the formation of the new stereocenter) also follows the general trend of ODHs, i.e., R-selectivity can be assumed in the reductive amination step based on experimental results with l -histidine.…”

“…The kinetic parameters of mODHs also align well with previous reports (Telek et al 2023 ) even though their catalytic efficiency compared to ArODH (which is at the higher end of the reported values) was found to be lower (Table 1 and 3 ). This might be an adverse effect of their increased stability which can compromise flexibility reflected in lower k cat values.…”

“…Aromatic side chains are generally not well tolerated by mODHs; however, l -histidine ( 2 ) is transformed with conversions comparable to Ar ODH, while mODH-48 is also capable of transforming 4-carboxy- l -phenylalanine ( 8 ) with moderate conversion. Opine dehydrogenases have strong enantiomer specificity towards l -amino acids (Telek et al 2023 ). mODHs share this feature as we could demonstrate by comparing conversions with d - and l -aspartate (data not shown).…”

“…Opine dehydrogenases (ODHs) represent a unique and yet largely underexplored class in this rapidly expanding landscape of biocatalysts for reductive amination (Telek et al 2023 ). They catalyze the coupling of α-ketoacids with α-amino acids yielding a variety of opine products.…”