Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China.
Biotechnol J. 2014 Mar;9(3):316-25. doi: 10.1002/biot.201200383. Epub 2014 Jan 29.
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.
天然产物仍然是当前临床药物和创新治疗药物的主要来源。由于野生型微生物只能少量产生天然产物，因此需要通过打破精确的遗传和生化电路来提高生产菌株的产量。在这里，我们以阿维菌素为例，通过合成生物学来提高产量和化学结构多样化。阿维菌素是由阿维链霉菌产生的大环内酯类化合物，因其抗寄生虫治疗而广为人知和广泛应用。鉴于该分子及其衍生物的重要性，人们已经付出了很多努力并采用了多种策略来提高阿维菌素的产量并产生新的活性类似物。本文综述了成功应用于开发天然产物生产菌株的合成策略，并讨论了提高阿维菌素产量的应用的未来前景。
