Interspecific Protoplast Fusion Between The Sirolimus Producer Streptomyces Hygroscopicus FC904-25 And The Tacrolimus Producer Streptomyces FCZ0311

Sirolimus and tacrolimus are now use as immunosuppressants to prevent and treat graftrejection in organ transplant and cure autoimmune diseases. Both compounds arenitrogen-containing macrolides. Sirolimus is a 36-membered macrocyclic lactone, whereastacrolimus is a 23-membered one. The biosynthetic pathways of two compounds may shareseveral common steps and may have somewhat differences.This topic carried out the main influence factors on protoplast formation andregeneration in Streptomyces hygroscopicus FC904-25 and Streptomyces FCZ0311respectively, and made sure the most suitable conditions of protoplast formation andregeneration from both different species of Streptomyces, respectively. The interspecificprotoplast fusion between Streptomyces hygroscopicus FC904-25 and StreptomycesFCZ0311 was studied and the green fusants having different cultural characteristics fromparent strains were obtained. The morphological and cultural characteristics of the fusantNo.9 as a candidate were studied. The susceptibility to antibiotics in the fusant No.9 wasdetermined. Under different conditions, the fermentation of the fusant No.9 was carried outand the culture broth was analysed by HPLC and LC-MS. The data showed that the greenfusant NO.9 also produced tacrolimus.