- 作者: 蕭明熙; 唐嘯石
- 作者服務機構: 榮民總醫院醫學研究部; 國防醫學院生化系
- 中文摘要:
美維諾林和堪培丁這二種真菌代謝物均因為能夠抑制哺乳類的膽固醇生物合成而受重視。二者的生物源都是由各含
十八碳與四碳的二條多羰鏈轉化而成,在美維諾林結構上C-2'與C-6的兩個甲基,亦已知是來自S-腺?甲硫胺酸。
為獲知兩處甲基移轉步驟的先後次序和時機,經液相培養真菌Aspergillus terreus (ATCC 20542),並預擇定代謝物
產生階段,置入含碳-14或氚/碳-14雙同位素標示的甲硫胺酸,使轉化成美維諾林。同位素標示進入美維諾林的程度和
雙同位素分配至C-2'和C-6兩處甲基的比,以化學裂解法確認。
本研究獲致以下結論:在美維諾林的生物合成途徑上,C-6處的甲基轉移在先,C-2'處者在後,而兩處甲基化反應
中,甲基所含的三個氫均自S-腺?甲硫胺酸完整地轉移過來。故推斷先後兩次的甲基化反應機轉均是將甲基整個移至碳
陰離子型的中間物。
a - 英文摘要: Mevinolin and compactin are fungal metabolites which inhibit cholesterol biosynthesis in mammaliansystems. Biogenetically, mevinolin is formed from polyketide chains, one 18-carbon and one 4-carbon,derived from acetate in normal head to tail fashion. The remaining two carbons in mevinolin, namely C-2'and C-6 methyl groups, are transferred from S-adenosylmethionine. To distinguish the timing and sequenceof these two methylation steps, (方程式無法摘錄) -and (方程式無法摘錄) -L-methionine were fed to Aspergillus terreusat several selected production intervals. Location and distribution of labels were determined by the specificchemical degradation methods. The results have demonstrated clearly that transfer of methyl groups from two S-adenosylmethio-nine molecules to the biosynthetic precursors of mevinolin was a sequential process. Methylation at C-6preceded that at C-2' of mevinolin. Both methylation steps proceeded with complete retention of hydro-gens. Methyl groups were probably transferred to the anion-like intermediates.
- 中文關鍵字: mevinolin; biosynthesis; isotope labeling; Aspergillus terreus
- 英文關鍵字: --