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Kojic acid is a remarkable secondary metabolite of Aspergillus with various hot spot applications in the field of medicine, cosmetics, food, agriculture, and chemistry field. However the needs of stable large production with safe cultures still need continuous searching. Microbial kojic acid concentrated highly on Aspergillus species especially Aspergillus flavus group. Ten isolates of A. flavus and A. oryzae isolated from various Egyptian sources were producible of KA in range 0.091±0.01 to 66.81± 0.95 g/l. Aspergillus oryzae (no. 4) that give maximum production was selected as non-toxinogenic safe isolate for optimizing the production by five levels CCD design of RSM. Maximum value of kojic acid with 108.4% increasing was 139.24 g/L (predicted 135.8 g/L) using glucose (+1; 200 g/l), yeast extract (+1; 6 g/l), KH2PO4, (+1; 1.5 g/l) and MgSO4.7H2O (+1; 1 g/l) through run (24). Model significance and validity tested by R2 values of KA was 0.987, DM 0.989 and CS 0.9831 and calculated with Derringer’s desirability function as 0.937. Optimized kojic acid showed stability against different range of heat stress from 40°C to 100°C during five continuous hours which may attribute that microbial product usually more stable than synthetic ones by attaching it with other active groups that guaranty more stability under stress conditions. Aspergillus oryzae (Ao-4) represents promising safe isolate for industrial kojic acid production with highly product stability using this significant valid experimental design.

AMEDMENT STABLE KOJIC ACID PRODUCED BY NON-TOXINOGENIC ASPERGILLUS ORYZAE USING FIVE LEVELS CENTRAL COMPOSITE DESIGN OF RESPONSE SURFACE METHODOLOGY