Dual Upcycling of Olive Leaves for the Biocatalytic Synthesis of Antioxidant Cortisone Derivatives

Bioconversion of cortisone leads to the synthesis of the steroid derivatives 1,9β,17,21- tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione (SCA) and 1,9β,17,20β,21- pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one (SCB), which have been identified as biologically active molecules in affections associated with oxidative stress and inflammation, particularly in the skin and eye. To date, the synthesis of SCA and SCB can only be achieved through a biocatalytic approach, following a biotransformation process catalyzed by Rhodococcus rhodnii DSM43960, a synthetic pathway that adheres to the principles of green chemistry. To further enhance the sustainability of this process, this study demonstrated that SCA and SCB can be synthesized by bioconversion in a complex medium derived from a dual upcycling process involving olive leaves (UOLM). By formulating a medium based on olive leaves, a by-product derived from the previously reported biotechnological production of lactic acid, and using a concentration of 10% v/v UOLM and 1 g/L cortisone at pH 7.5, bioconversion yields of 90 ± 4.5% were achieved, with a predominance of SCB. Investigations into the addition of supplements, such as tryptone, peptone, and corn steep liquor (CSL), to assess potential improvements in yield were conducted, but no significant positive variations were observed. For the first time, bioactive steroidswere synthesized fromamediumobtained through a dual upcycling process of olive leaves, introducing an innovativemethod that opens new possibilities for the investigation of a second generation of biosteroids synthesized from lignocellulosic feedstocks.