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

The effect of divalent metal ions (i.e., Mn(2+), Mg(2+), Zn(2+), Cu(2+), and Co(2+)) 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 Mg(2+) was found to be the most effective. Under the optimal condition of Mg(2+) 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 Mg(2+) 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.