Youderian P, Lawes M C, Creighton C, Cook J C, Saier M H
Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, Idaho 83844-3052, USA.
J Bacteriol. 1999 Apr;181(7):2225-35. doi: 10.1128/JB.181.7.2225-2235.1999.
The glucose analog 2-deoxyglucose (2dGlc) inhibits the growth and multicellular development of Myxococcus xanthus. Mutants of M. xanthus resistant to 2dGlc, designated hex mutants, arise at a low spontaneous frequency. Expression of the Escherichia coli glk (glucokinase) gene in M. xanthus hex mutants restores 2dGlc sensitivity, suggesting that these mutants arise upon the loss of a soluble hexokinase function that phosphorylates 2dGlc to form the toxic intermediate, 2-deoxyglucose-6-phosphate. Enzyme assays of M. xanthus extracts reveal a soluble hexokinase (ATP:D-hexose-6-phosphotransferase; EC 2.7.1.1) activity but no phosphotransferase system activities. The hex mutants have lower levels of hexokinase activities than the wild type, and the levels of hexokinase activity exhibited by the hex mutants are inversely correlated with the ability of 2dGlc to inhibit their growth and sporulation. Both 2dGlc and N-acetylglucosamine act as inhibitors of glucose turnover by the M. xanthus hexokinase in vitro, consistent with the finding that glucose and N-acetylglucosamine can antagonize the toxic effects of 2dGlc in vivo.
葡萄糖类似物2-脱氧葡萄糖(2dGlc)可抑制黄色粘球菌的生长和多细胞发育。对2dGlc具有抗性的黄色粘球菌突变体,称为hex突变体,以较低的自发频率出现。在黄色粘球菌hex突变体中表达大肠杆菌glk(葡萄糖激酶)基因可恢复对2dGlc的敏感性,这表明这些突变体是由于可溶性己糖激酶功能丧失而产生的,该功能可将2dGlc磷酸化形成有毒中间体2-脱氧葡萄糖-6-磷酸。黄色粘球菌提取物的酶分析显示有可溶性己糖激酶(ATP:D-己糖-6-磷酸转移酶;EC 2.7.1.1)活性,但没有磷酸转移酶系统活性。hex突变体的己糖激酶活性水平低于野生型,并且hex突变体表现出的己糖激酶活性水平与2dGlc抑制其生长和孢子形成的能力呈负相关。在体外,2dGlc和N-乙酰葡糖胺均作为黄色粘球菌己糖激酶的葡萄糖周转抑制剂,这与葡萄糖和N-乙酰葡糖胺可在体内拮抗2dGlc的毒性作用这一发现一致。