Recently discovered endogenous mammalian lipids fatty
acid esters of hydroxy fatty acids (FAHFAs), proved to <a></a><a>have anti-inflammatory
and anti-diabetic effects</a>. Due to their extremely low abundancies <i>in vivo</i>, forging a feasible scenario for
FAHFA synthesis is critical for their use in uncovering biological mechanism or
clinical trials. Here, we showcase a fully enzymatic approach, a novel <i>in vitro</i> bi-enzymatic cascade system, enabling
an effective conversion of nature-abundant fatty acid into FAHFAs. Two
hydratases <a></a><a>from <i>L. acidophilus</i> </a>were
used for converting unsaturated fatty acids to various stereospecific hydroxy
fatty acids, followed by esterification with another fatty acid catalyzed by <i>C.
antarctica</i> lipase A (CALA). Various FAHFAs were synthesized in a
preparative scale using this bi-enzymatic approach in a one-pot two-step
operation mode. In all, we demonstrated that hydratase-CALA system promises a
sustainable solution to the synthesis of structure-diverse stereospecific
FAHFAs.