Abstract

Kojic acid is widely used to inhibit the browning effect of tyrosinase in cosmetic and food industries. In this work, synthesis of kojic monooleate ester (KMO) was carried out using lipase-catalysed esterification of kojic acid and oleic acid in a solvent-free system. Response Surface Methodology (RSM) based on central composite rotatable design (CCRD) was used to optimise the main important reaction variables, such as enzyme amount, reaction temperature, substrate molar ratio, and reaction time along with immobilised lipase from Candida Antarctica (Novozym 435) as a biocatalyst. The RSM data indicated that the reaction temperature was less significant in comparison to other factors for the production of a KMO ester. By using this statistical analysis, a quadratic model was developed in order to correlate the preparation variable to the response (reaction yield). The optimum conditions for the enzymatic synthesis of KMO were as follows: an enzyme amount of 2.0 wt%, reaction temperature of 83.69°C, substrate molar ratio of 1:2.37 (mmole kojic acid:oleic acid) and a reaction time of 300.0 min. Under these conditions, the actual yield percentage obtained was 42.09%, which is comparably well with the maximum predicted value of 44.46%. Under the optimal conditions, Novozym 435 could be reused for 5 cycles for KMO production percentage yield of at least 40%. The results demonstrated that statistical analysis using RSM can be used efficiently to optimise the production of a KMO ester. Moreover, the optimum conditions obtained can be applied to scale-up the process and minimise the cost.

Highlights

  • Kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) is an antibiotic produced by many species of Aspergillus, Acetobacter and Penicillium in an aerobic process utilizing a wide range of carbon sources [1]

  • The results reported that kojic acid esters were safe and nontoxic depigmenting agents with a satisfactory inhibitory effect on tyrosinase activity as determined in B16F1 melanoma cells

  • In order to obtain a proper model for optimisation of kojic monooleate (KMO) ester synthesis in a solvent-free system, the central composite rotatable design (CCRD), which is the best design for response surface optimisation, was selected with four factors five levels including reaction temperature, reaction time, enzyme amount, and substrate molar ratio

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Summary

Introduction

Kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) is an antibiotic produced by many species of Aspergillus, Acetobacter and Penicillium in an aerobic process utilizing a wide range of carbon sources [1]. Kojic acid can be used as a skin-lightening or bleaching agent in cosmetic preparations [2,3]. This natural compound is not a very stable compound and when exposed to the sun or air, it will lose its effectiveness as a skin care product. The results reported that kojic acid esters were safe and nontoxic depigmenting agents with a satisfactory inhibitory effect on tyrosinase activity as determined in B16F1 melanoma cells. These compounds have potential to be used in cosmetic formulation. In order to improve the lipophilic properties of kojic acid, modification through esterification with fatty acids is the ideal method to synthesize kojic acid esters [5,6,7]

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