Enhanced production of ansamitocin P-3 by addition of Mg2+ in fermentation of Actinosynnema pretiosum

The effect of divalent metal ions (i.e., Mn2+, Mg2+, Zn2+, Cu2+, and Co2+) on the production of anticancer ansamitocin P-3 (AP-3) by submerged cultures of Actinosynnema pretiosum in medium containing agro-industrial residues was investigated, and Mg2+ was found to be the most effective. Under the optimal condition of Mg2+ addition, the maximal AP-3 production titer reached 85 mg/L, which was 3.0-fold that of the control. The activities of methylmalonyl-CoA carboxyltransferase (MCT) and methylmalonyl-CoA mutase (MCM) were enhanced. The content of two precursors, malonyl-CoA and methylmalonyl-CoA, was lower than that of control. This work demonstrates that Mg2+ addition is a simple and effective strategy for increasing AP-3 production through the regulation of enzyme activity and pools of precursors. The information obtained can be helpful to its efficient production on large scale.