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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.

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SWWO is made up of four parts. The first part is to initialize population and a new initialization sequence method is proposed, named NEH_COV, the time complexity of initialization is 𝑂(𝑛 2 ). The second part is the propagation operation.Based on the block-shift operation, the modified BSO, named MBSO, is proposed.The time complexity of the second part is 𝑂(𝑛 2 ). The third part is the refraction operation. There is only one water wave in SWWO. A new solution is obtained by crossing the historical optimal solution with the current solution. The time complexity is 𝑂(𝑚𝑛). The fourth part is the breaking operation. By executing an improved variable neighborhood search, named MVNS, the time complexity is 𝑂(2𝑛 2 ) .According to the analyses above, the time complexity of SWWO under the condition of k times iteration is calculated as follows. 𝑂(𝑘, 𝑚 S2. Evaluation CriterionIn order to demonstrate the effectiveness of our proposed algorithm and compare the performance with other approaches visually, the average relative percentage deviation (ARPD) was applied to measure the quality of the experimental results. The calculation formula of ARPD is as follows:* * 1