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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Clavulanic acid production by Streptomyces clavuligerus: Biogenesis, regulation and strain improvement
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Clavulanic acid production by Streptomyces clavuligerus: Biogenesis, regulation and strain improvement

机译：克拉维链霉菌生产克拉维酸的生物发生，调控和菌株改良

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摘要

Clavulanic acid (CA) is a potent β-lactamase inhibitor produced by Streptomyces clavuligerus and has been successfully used in combination with β-lactam antibiotics (for example, Augmentin) to treat infections caused by β-lactamase-producing pathogens. Since the discovery of CA in the late 1970s, significant information has accumulated on its biosynthesis, and regarding molecular mechanisms involved in the regulation of its production. Notably, the genes directing CA biosynthesis are clustered along with the genes responsible for the biosynthesis of the β-lactam antibiotic, cephamycin C, and co-regulated, which makes this organism unique in that the production of an antibiotic and production of a small molecule to protect the antibiotic from its enzymatic degradation are controlled by shared mechanisms. Traditionally, the industrial strain improvement programs have relied significantly on random mutagenesis and selection approach. However, the recent availability of the genome sequence of S. clavuligerus along with the capability to build metabolic models, and ability to engineer the organism by directed approaches, has created exciting opportunities to improve strain productivity more efficiently. This review will include focus mainly on the gene organization of the CA biosynthetic genes, regulatory mechanisms that affect its production, and will include perspectives on improving strain productivity.
机译：棒酸（CA）是由链霉菌产生的有效的β-内酰胺酶抑制剂，已成功与β-内酰胺抗生素（例如Augmentin）联合使用，以治疗由产生β-内酰胺酶的病原体引起的感染。自从1970年代后期发现CA以来，已经积累了有关其生物合成以及有关调节其生产的分子机制的大量信息。值得注意的是，指导CA生物合成的基因与负责β-内酰胺抗生素，头孢霉素C生物合成的基因聚集在一起，并且受到共同调节，这使得该生物体的独特之处在于产生抗生素和产生小分子。保护抗生素免于其酶促降解受共同机制控制。传统上，工业菌株改良计划很大程度上依赖于随机诱变和选择方法。然而，近来克拉维链球菌基因组序列的可用性以及建立代谢模型的能力，以及通过定向方法对生物体进行工程改造的能力，为提高菌株生产率提供了令人兴奋的机会。这次审查将主要集中在CA生物合成基因的基因组织，影响其生产的调控机制上，并包括改善菌株生产力的观点。

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