Tacrolimus - Strategies for Enhancing Tacrolimus Production at the Classical and Transcriptional Level

Tacrolimus (FK506) is a 23 membered polyketide macrolide, a potent immunosuppressant, and a useful secondary metabolite that exhibits 10 - 100 times more efficient than cyclosporine. It becomes an important therapeutic drug not only in transplantation but also used frequently in the treatment of severe atopic dermatitis, and secondary lymphedema. Biosynthesis of Tacrolimus is a multifaceted process involved in many essential pathways, but low productivity of tacrolimus fromStreptomyces sp. is a major concern regarding its increased global demand. To boost Tacrolimus production, many steps such as alteration in the biosynthetic pathway, strain improvements, optimizing culture conditions, and use of tacrolimus precursors have been adapted. This review focuses on different approaches at the nutritional and genetic engineering level to scale up the titer of tacrolimus.