P-2 14員環マクロライド抗生物質ランカマイシンのスターターユニットおよび水酸化反応の解析(ポスター発表の部)

概要

論文の詳細を見る
The biosynthetic gene cluster of lankamycin (LM), a 14-membered macrolide antibiotic, is coded on the 210-kb linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. LM contains a 3-hydroxy-2-butyl group at the C-13 position, which is different from an ethyl group in erythromycin. The branched chain at the C-13 position corresponds to a starter unit in polyketide biosynthesis, therefore, 3-hydroxy-2-butyrate or its equivalent such as isoleucine are considered as the starter in LM biosynthesis. This was confirmed by incorporation of deuterium in [3-^2H]DL-isoleucine into the C-14 position of LM. The timing of hydroxylation reactions at the C-15 and C-8 positions of LM was studied by constructing disruptants of two P450-hydroxylase genes, IkmF and IkmK. The IkmF disruptant produced 8-deoxylankamycin, while the IkmK disruptant produced both 15-deoxylankamycin and 8,15-dideoxylankamycin. These results indicated that LkmF is C-8 hydroxylase and LkmK is C-15 hydroxylase in LM biosynthesis, and in addition suggested the order of hydroxylation steps; namely, hydroxylation may occur at first at C-15 by LkmK and then at C-8 by LkmF. In vitro bioconversion experiments showed that the LkmK protein could hydroxylate 15-deoxyLM and 8,15-dideoxyLM to LM and 8-deoxyLM, respectively. However, 8-deoxyLM was not converted to LM by LkmF, suggesting its strict substrate specificity. To test the effect of two sugar moietirs on hydroxylation reactions, glycosyltransferase genes, IkmI and IkmL, were disrupted. Gene disruptants of IkmI and IkmL accumulated 3-L-arcanosyllankanolide and 15-oxo-8-deoxylankanolide, respectively, which strongly suggested that a C-8 hydroxylation occurs after the glycosylation event on the C-3 position.
天然有機化合物討論会の論文
2006-09-15

P-2 14員環マクロライド抗生物質ランカマイシンのスターターユニットおよび水酸化反応の解析(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク