Biocatalysis offers a complementary approach with the potential for an exceptional selectivity and safety profile, but must contend with the rarity of fluorine in the biosphere. No enzymes are known to perform electrophilic fluorination, and only one has been found to perform nucleophilic fluorination on a highly activated substrate. Thus, the strategy of using promiscuous enzymes to elaborate upon simple opticallyinactive organofluorine building blocks has been adopted to construct C-F stereocenters. For example, stereogenic secondary fluorides (R1-CFH-R2) have been prepared by our group and others, exploiting pyruvate aldolases that utilize fluoropyruvate as a non-native donor substrate (Figure ). Fluorine can be rendered in either stereochemistry depending on the specific structural family of the aldolase, but the switch to a fluoro-donor typically restricts the acceptor scope to a small set of highly polar aldehydes due to the origin of these enzymes in carbohydrate metabolism. Enzymatic preparation of stereogenic tertiary fluorides (R1-CFR2-R3) has been accomplished with lipase-catalyzed kinetic resolution and desymmetrization (Figure ), but provided modest stereoselectivity and reaction diversity. In this work, we investigated the type II pyruvate aldolase HpcH and its engineered variants and assessed their ability to catalyze aldol addition of ß-fluoro-α-ketoacids to diverse aldehydes (Figure ). As a result, we now report the first example to our knowledge of asymmetric synthesis of tertiary fluorides by enzymatic C-C bond formation.