Walker J B
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77251.
J Bacteriol. 1990 Oct;172(10):5844-51. doi: 10.1128/jb.172.10.5844-5851.1990.
Bluensomycin (glebomycin) is an aminocyclitol antibiotic that differs structurally from dihydrostreptomycin in having bluensidine (1D-1-O-carbamoyl-3-guanidinodeoxy-scyllo-inositol) rather than streptidine (1,3-diguanidino-1,3-dideoxy-scyllo-inositol) as its aminocyclitol moiety. Extracts of the bluensomycin producer Streptomyces hygroscopicus form glebosus ATCC 14607 (S. glebosus) were found to have aminodeoxy-scyllo-inositol kinase activity but to lack 1D-1-guanidino-3-amino-1,3-dideoxy-scyllo-inositol kinase activity, showing for the first time that these two reactions in streptomycin producers must be catalyzed by different enzymes. S. glebosus extracts therefore possess the same five enzymes required for synthesis of guanidinodeoxy-scyllo-inositol from myo-inositol that are found in streptomycin producers but lack the next three of the four enzymes found in streptomycin producers that are required to synthesize the second guanidino group of streptidine-P. In place of a second guanidino group, S. glebosus extracts were found to catalyze a Mg2(+)-dependent carbamoylation of guanidinodeoxy-scyllo-inositol to form bluensidine, followed by a phosphorylation to form bluensidine-P. The novel carbamoyl-P:guanidinodeoxy-scyllo-inositol O-carbamoyltransferase and ATP:bluensidine phosphotransferase activities were not detected in streptomycin producers or in S. glebosus during its early rapid growth phase. Free bluensidine appears to be a normal intermediate in bluensomycin biosynthesis, in contrast to the case of streptomycin biosynthesis; in the latter, although exogenous streptidine can enter the pathway via streptidine-P, free streptidine is not an intermediate in the endogenous biosynthetic pathway. Comparison of the streptomycin and bluensomycin biosynthetic pathways provides a unique opportunity to evaluate those proposed mechanisms for the evolutionary acquisition of new biosynthetic capabilities that involve gene duplication and subsequent mutational changes in one member of the pair. In this model, there are at least five pairs of enzymes catalyzing analogous reactions that can be analyzed for homology at both the protein and DNA levels, including two putative pairs of inositol kinases detected in this study.
蓝霉素（格莱博霉素）是一种氨基环醇抗生素，其结构与二氢链霉素不同，它的氨基环醇部分是蓝霉素idine（1D-1-O-氨基甲酰基-3-胍基脱氧-scyllo-肌醇）而不是链霉idine（1,3-二胍基-1,3-二脱氧-scyllo-肌醇）。发现蓝霉素产生菌吸水链霉菌格莱博亚种ATCC 14607（格莱博链霉菌）的提取物具有氨基脱氧-scyllo-肌醇激酶活性，但缺乏1D-1-胍基-3-氨基-1,3-二脱氧-scyllo-肌醇激酶活性，这首次表明链霉素产生菌中的这两个反应必须由不同的酶催化。因此，格莱博链霉菌提取物具有与链霉素产生菌中相同的五种从肌醇合成胍基脱氧-scyllo-肌醇所需的酶，但缺乏链霉素产生菌中用于合成链霉idine-P的第二个胍基所需的四种酶中的后三种。代替第二个胍基，发现格莱博链霉菌提取物催化胍基脱氧-scyllo-肌醇的Mg2(+)-依赖性氨基甲酰化反应形成蓝霉素idine，随后进行磷酸化反应形成蓝霉素idine-P。在链霉素产生菌或格莱博链霉菌早期快速生长阶段未检测到新的氨基甲酰磷酸：胍基脱氧-scyllo-肌醇O-氨基甲酰转移酶和ATP：蓝霉素idine磷酸转移酶活性。与链霉素生物合成的情况相反，游离蓝霉素idine似乎是蓝霉素生物合成中的正常中间体；在后者中，虽然外源链霉idine可以通过链霉idine-P进入途径，但游离链霉idine不是内源性生物合成途径中的中间体。链霉素和蓝霉素生物合成途径的比较提供了一个独特的机会来评估那些提出的涉及基因复制以及随后该对中的一个成员发生突变变化的新生物合成能力进化获得机制。在这个模型中，至少有五对催化类似反应的酶，可以在蛋白质和DNA水平上分析它们的同源性，包括本研究中检测到的两对假定的肌醇激酶。
