HHDHs belong to the superfamily of short-chain dehydrogenases/reductases and are distinguished by characteristic sequence motifs, including a Ser-Tyr-Arg catalytic triad . Since the identification of HheG and HheG2 by database mining in 2014 and 2017, respectively, advances in sequencing technology have expanded the available sequence space considerably. Accordingly, mining this expanded sequence space for putative HHDH sequences based on known sequence motifs and classification of the hits into phylogenetic subtypes yielded a new member of the G subtype, HheG3 from Actinobacteria bacterium. This enzyme exhibits 70% sequence identity with HheG and alignment of the protein sequences indicates a high degree of conservation around the catalytic triad and firstsphere residues (Figure ). Structural predictions by AlphaFold2 suggest a very similar tertiary structure of HheG3 compared to HheG and HheG2 (except for the flexible loop unique to the G-type HHDDs), all of which agree well with the experimental crystal structure of HheG 22 (Figure ). In analogy to its relatives , HheG3 possesses almost no dehalogenation activity with a variety of chloroalcohols but proved highly active in the nucleophilic ring opening of the cyclic epoxide 1 with azide (Figure ), confirming HheG3's classification as a G-type HHDH.