Biological/fermentative production pathway

In avermectin Bl, there is a double bond between C-22 and C-23, whereas in avermectin B2 R OH. The product ratio of B2 to Bl is 1.6 1. Since the Bl analog is much more effective as an antiparasite, there is a desire to improve the B1 B2 ratio, which can be achieved by a dehydratase domain [88, 89]. Its directed evolution and mutant screening led to a mutant giving an excellent fermentation titer of Bl B2 = 1 0.07 [90, 91]. As a result of understanding the biosynthesis, pathway engineering, and directed evolution, a biologically superior new product, doramectin (Dectomax ), was evolved from a mixture of eight natural products. 

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