Barbuto Ferraiuolo Simona, Cammarota Marcella, Schiraldi Chiara, Restaino Odile Francesca
Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.
Appl Microbiol Biotechnol. 2021 Jan;105(2):551-568. doi: 10.1007/s00253-020-11064-2. Epub 2021 Jan 4.
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.
链霉菌是生物技术应用中用途最为广泛的属之一，被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，需要多学科方法来研究，但综述文章通常仅报道了诸如新菌株和代谢产物的分离、形态学研究以及遗传或代谢研究等单一方面的研究。此外，即使链霉菌在工业中被广泛使用，但很少有综述文章关注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定的关键参数。本小型综述广泛阐述了链霉菌在抗生素、免疫抑制剂、抗癌药物、甾体药物和驱虫剂的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，重点关注工艺开发方面，描述了为提高产量而使用的不同方法和技术。描述了营养物质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与代谢工程和用于菌株改良的遗传工具相结合的生物技术策略。还报道了在非常规载体上使用完整细胞、游离细胞和固定化细胞进行药物生物转化过程。本文报道了过去8年发表的最杰出的30项研究，同时阐述了该领域生物技术研究的未来趋势和前景。要点：• 报道了链霉菌用于药物生产的最新生物技术过程。• 综述了基于链霉菌的药物生物转化的创新方法。• 关于提高次级代谢产物产量的发酵和基因组系统的新进展。
