Effect of culture pH and media composition on the ratio of tcicoplanin $A_1$ and $A_2$ biosynthesis

Teicoplanin is a glycopeptide antibiotic produced by Actinoplanes teichomyceticus novo sp. A TCC 31121. It is active against Gram-positive bacteria and it is under evaluation for use in man. Teicoplanin mixture in fermentation broth contains major amounts of teicoplanin $A_1$ and $A_2$ and a minor amount tcicoplanin of $A_3$. Commercial teicoplanin product is composed of five major components of very similar polarity, designated T-$A_2$-l, 2, 3, 4 and 5, and the more polor component, designated T -$A_3$. The culture conditions were studied in order that hydrophilic teicoplanin $A_2$ components are more produced but hydrophobic teicoplanin $A_1$ with lower bioactivity are less produced in submerged culture. Effects of culture pH and nutrients on the biosynthes ratio of teicoplanin $A_1$ and $A_2$ were confirmed in flask culture using MOPS buffer system through TLC, bioautography and bioassay. It was elucidated that optimal pH is 7.4 for teicoplanin $A_2$ biosynthesis but is 5.2 for teicoplanin $A_1$ biosynthesis, and that trace elements stimulate $A_2$ production but malt extract stimulate $A_1$production.