Abstract

Streptomyces is one of the most versatile genera for biotechnological applications, widely employed as platform in the production of drugs. Although streptomycetes have a complex life cycle and metabolism that would need multidisciplinary approaches, review papers have generally reported only studies on single aspects like the isolation of new strains and metabolites, morphology investigations, and genetic or metabolic studies. Besides, even if streptomycetes are extensively used in industry, very few review papers have focused their attention on the technical aspects of biotechnological processes of drug production and bioconversion and on the key parameters that have to be set up. This mini-review extensively illustrates the most innovative developments and progresses in biotechnological production and bioconversion processes of antibiotics, immunosuppressant, anticancer, steroidal drugs, and anthelmintic agents by streptomycetes, focusing on the process development aspects, describing the different approaches and technologies used in order to improve the production yields. The influence of nutrients and oxygen on streptomycetes metabolism, new fed-batch fermentation strategies, innovative precursor supplementation approaches, and specific bioreactor design as well as biotechnological strategies coupled with metabolic engineering and genetic tools for strain improvement is described. The use of whole, free, and immobilized cells on unusual supports was also reported for bioconversion processes of drugs. The most outstanding thirty investigations published in the last 8 years are here reported while future trends and perspectives of biotechnological research in the field have been illustrated.

Key points

• Updated Streptomyces biotechnological processes for drug production are reported.

• Innovative approaches for Streptomyces-based biotransformation of drugs are reviewed.

• News about fermentation and genome systems to enhance secondary metabolite production.

中文翻译：

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链霉菌作为药物生物技术生产过程的平台

摘要

链霉菌是生物技术应用最通用的属之一，广泛用作药物生产的平台。尽管链霉菌具有复杂的生命周期和新陈代谢，需要多学科的方法，但综述论文通常只报道了单一方面的研究，如新菌株和代谢物的分离、形态学研究以及遗传或代谢研究。此外，即使链霉菌在工业中得到广泛应用，也很少有综述文章将注意力集中在药物生产和生物转化的生物技术过程的技术方面以及必须设置的关键参数上。这篇小型评论广泛地说明了抗生素生物技术生产和生物转化过程中最具创新性的发展和进展，链霉菌的免疫抑制剂、抗癌剂、甾体药物和驱虫剂，重点介绍了工艺开发方面，描述了为提高产量而使用的不同方法和技术。描述了营养和氧气对链霉菌代谢的影响、新的补料分批发酵策略、创新的前体补充方法、特定的生物反应器设计以及生物技术策略以及代谢工程和遗传工具用于菌株改良的方法。还报道了在不寻常的支持物上使用完整的、游离的和固定的细胞用于药物的生物转化过程。

关键点

•报告了用于药物生产的最新链霉菌生物技术工艺。

•回顾了基于链霉菌的药物生物转化的创新方法。

•关于提高次生代谢产物生产的发酵和基因组系统的新闻。