Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan.
Chembiochem. 2012 Jul 9;13(10):1447-57. doi: 10.1002/cbic.201200149. Epub 2012 Jun 14.
New signaling molecules that induce lankacidin and lankamycin production in Streptomyces rochei were extracted from the culture filtrate and purified by Sephadex LH20 and silica gel chromatography with the help of bioassay. Chiral HPLC and ESI-MS analyses indicated the presence of two active components--SRB1 and SRB2--and their molecular formulas were established to be C15H24O5 and C16H26O5, respectively. By extensive NMR analysis, SRB1 and SRB2 were determined to be 2-(1'-hydroxy-6'-oxo-8'-methylnonyl)-3-methyl-4-hydroxybut-2-en-1,4-olide and 2-(1'-hydroxy-6'-oxo-8'-methyldecyl)-3-methyl-4-hydroxybut-2-en-1,4-olide, respectively. These structures were finally confirmed by chemical synthesis and the absolute configuration at C-1' was determined to be R in each case. The synthetic 1'R isomers induced production of lankacidin and lankamycin at around 40 nM concentrations. SRB1 and SRB2 are therefore distinct from the well-known 2,3-disubstituted γ-butyrolactone molecules such as A-factor, virginia butanolide, and SCB1 and and belong, like avenolide, recently isolated from Streptomyces avermitilis, to the γ-butenolide family.
从罗氏链霉菌的发酵滤液中提取了诱导朗卡菌素和兰卡霉素产生的新信号分子，并通过生物测定用 Sephadex LH20 和硅胶色谱法进行了分离和纯化。手性 HPLC 和 ESI-MS 分析表明存在两种活性成分——SRB1 和 SRB2——它们的分子式分别为 C15H24O5 和 C16H26O5。通过广泛的 NMR 分析，确定 SRB1 和 SRB2 分别为 2-(1'-羟基-6'-酮-8'-甲基壬基)-3-甲基-4-羟基丁-2-烯-1,4-内酯和 2-(1'-羟基-6'-酮-8'-甲基癸基)-3-甲基-4-羟基丁-2-烯-1,4-内酯。这些结构最终通过化学合成得到证实，并且在每种情况下 C-1'的绝对构型均被确定为 R。合成的 1'R 异构体在约 40 nM 浓度下诱导朗卡菌素和兰卡霉素的产生。因此，SRB1 和 SRB2 与众所周知的 2,3-二取代 γ-丁内酯分子（如 A 因子、维吉尼亚丁内酯和 SCB1）不同，与最近从链霉菌属中分离出的avenolide 一样，属于 γ-丁烯内酯家族。
