Effect of pH on biosynthesis of lovastatin and other secondary metabolites by Aspergillus terreus ATCC 20542

The effect of the initial pH value of the cultivation medium on lovastatin (mevinolinic acid) biosynthesis by Aspergillus terreus ATCC20542 was studied. It was found that if the pH value of the broth is acidic, the direct chromatographic assay of mevinolinic acid leads to the underestimated values. Thus, the equilibrium curve was determined for the transformation of β-hydroxy acid form of lovastatin (mevinolinic acid) into lovastatin lactone. The calculation of the equilibrium constant shows that when the pH value of the solution is 4.98, concentrations of both forms of lovastatin are equal to each other. This finding was next used to study mevinolinic acid formation at the various initial pH values of the medium. It occurs that even at pH lower than 5.5 mevinolinic acid is still, although inefficiently, produced and its presence remains unnoticed, unless the samples of the broth are alkalised prior to the assay. Mevinolinic acid is efficiently produced at the initial pH value of the medium equal to 7.5 and 8.5 and it correlates with the rapid utilisation of lactose by A. terreus. Additionally, other secondary metabolites were sought at the various initial pH values of the medium with the use of mass spectrometry. (+)-Geodin is only formed at pH 6.5, while monacolin L is found at the highest amount at pH 7.5.

► At pH < 6 direct assay of mevinolinic acid leads to underestimated results.
► Direct analysis of mevinolinic acid in the broth requires sample alkalisation.
► At pH ≥ 6.5 the highest titres of mevinolinic acid are obtained, achieving maximum at 7.5.
► pH level influences lactose uptake kinetics by Aspergillus terreus.
► Apart from mevinolinic acid, dependent on pH, monacolin L and (+)-geodin are formed.