López-Agudelo Víctor A, Gómez-Ríos David, Ramirez-Malule Howard
Escuela de Ingeniería Química, Universidad del Valle, A.A., Cali 25360, Colombia.
Grupo de Investigación en Simulación, Diseño, Control y Optimización de Procesos (SIDCOP), Departamento de Ingeniería Química, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín 050010, Colombia.
Antibiotics (Basel). 2021 Jan 18;10(1):84. doi: 10.3390/antibiotics10010084.
Clavulanic acid (CA) is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by (). CA is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin, conferring them high potential to treat diseases caused by bacteria that possess β‑lactam resistance. The clinical importance of CA and the complexity of the production process motivate improvements from an interdisciplinary standpoint by integrating metabolic engineering strategies and knowledge on metabolic and regulatory events through systems biology and multi-omics approaches. In the large-scale bioprocessing, optimization of culture conditions, bioreactor design, agitation regime, as well as advances in CA separation and purification are required to improve the cost structure associated to CA production. This review presents the recent insights in CA production by , emphasizing on systems biology approaches, strain engineering, and downstream processing.
克拉维酸（CA）是一种由（）产生的具有弱抗菌活性的不可逆β-内酰胺酶抑制剂。CA通常与广谱β-内酰胺抗生素如阿莫西林联合配制，使其具有治疗由具有β-内酰胺抗性的细菌引起的疾病的高潜力。CA的临床重要性和生产过程的复杂性促使从跨学科角度进行改进，通过系统生物学和多组学方法整合代谢工程策略以及关于代谢和调控事件的知识。在大规模生物加工中，需要优化培养条件、生物反应器设计、搅拌方式以及CA分离和纯化方面的进展，以改善与CA生产相关的成本结构。本综述介绍了（）生产CA的最新见解，重点关注系统生物学方法、菌株工程和下游加工。
