Synthetic biology of avermectin for production improvement and structure diversification

Natural products are still key sources of current clinical drugs and innovative therapeutic agents. Since wild-type microorganisms only produce natural products in very small quantities, yields of production strains need to be improved by breaking down the precise genetic and biochemical circuitry. Herein, we use avermectins as an example of production improvement and chemical structure diversification by synthetic biology. Avermectins are macrocyclic lactones produced by Streptomyces avermitilis and are well known and widely used for antiparasitic therapy. Given the importance of this molecule and its derivatives, many efforts and strategies were employed to improve avermectin production and generate new active analogues. This review describes the current status of synthetic strategies successfully applied for developing natural-product-producing strains and discusses future prospects for the application of enhanced avermectin production.