Kurumbang Nagendra Prasad, Oh Tae-Jin, Liou Kwangkyoung, Sohng Jae Kyung
Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Asan 336-708, Korea.
J Microbiol Biotechnol. 2008 May;18(5):866-73.
2-Deoxystreptamine is a core aglycon that is vital to backbone formation in various aminoglycosides. This core structure can be modified to develop hybrid types of aminoglycoside antibiotics. We obtained three genes responsible for 2-deoxystreptamine production, neo7, neo6, and neo5, which encode 2-deoxy-scyllo-inosose synthase, L-glutamine: 2-deoxy-scyllo-inosose aminotransferase, and dehydrogenase, respectively, from the neomycin gene cluster. These genes were cloned into pIBR25, a Streptomyces expression vector, resulting in pNDOS. The recombinant pNDOS was transformed into a non-aminoglycoside-producing host, Streptomyces venezuelae YJ003, for heterologous expression. Based on comparisons of the retention time on LC-ESI/MS and ESIMS data with those of the 2-deoxystreptamine standard, a compound produced by S. venezuelae YJ003/pNDOS was found to be 2-deoxystreptamine.
2-脱氧链霉胺是一种核心苷元，对各种氨基糖苷类药物的骨架形成至关重要。这种核心结构可以进行修饰以开发混合型氨基糖苷类抗生素。我们从新霉素基因簇中获得了三个负责2-脱氧链霉胺产生的基因，即neo7、neo6和neo5，它们分别编码2-脱氧-异丝氨酸合成酶、L-谷氨酰胺：2-脱氧-异丝氨酸转氨酶和脱氢酶。这些基因被克隆到链霉菌表达载体pIBR25中，得到pNDOS。将重组pNDOS转化到不产生氨基糖苷类药物的宿主委内瑞拉链霉菌YJ003中进行异源表达。通过比较LC-ESI/MS和ESIMS数据上的保留时间与2-脱氧链霉胺标准品的保留时间，发现委内瑞拉链霉菌YJ003/pNDOS产生的一种化合物是2-脱氧链霉胺。
