Application of Plackett–Burman Design for Medium Constituents Optimization for the Production of L- phenylacetylcarbinol (L-PAC) by Saccharomyces Cerevisiae

Abstract

L-phenylacetylcarbinol (L-PAC) is an intermediate in the production of L-ephedrine and pseudoephedrine, which are pharmaceutical compounds used as decongestants and anti-asthmatics. L-PAC can be produced by chemical synthesis from cyanohydrins but the biotransformation route for its production from benzaldehyde is preferred industrially. This work aims to select the best culture medium and process conditions to produce L-PAC in shake flasks and 1 L bioreactor. Statistical experimental designs were applied for the optimization of medium constituents for L-PAC production by Saccharomyces cerevisiae. The production medium (PM) contained initially (grams per liter) glucose 25, peptone 20, yeast extract 10; MgSO₄.7H₂O 1; CaCl₂.2H₂O 0.05, Na₂HPO₄.12H₂O 35, citric acid 10.7 and Benzaldehyde 1. Using Plackett–Burman design (PB-12), peptone, citric acid and Na₂HPO₄.12H₂O were identified as significant variables which highly influenced L-PAC production. The optimum medium (OM) was constituted by glucose 40, peptone 5, yeast extract 10; MgSO₄.7H₂O 5; CaCl₂.2H₂O 0.01, Na₂HPO₄.12H₂O 35, citric acid 2 and Benzaldehyde 4. In this optimum condition L-PAC production was 4.92 g/L. Using this medium constitution, in bioreactor it was possible to obtain 7.5 g/L of L-PAC. This result was 44% superior than with the medium without optimization.