Optimization of a biotransformation process to produce 4-(2,3,5,6-tetramethylpyrazine-1)-4¡ä-demethylepipodophyllotoxin

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• 作者：Wei Zhao^a ; Hong-Mei Li^a ; Ya-Ling Tang^c ; Xin-Hua Liang^c ; Duan-Ji Wan^a ; Ya-Jie Tang^a ; ^b ; ^{yajietang@hotmail.com} ; ^{yajietang@yahoo.com.cn}
• 关键词：Biotransformation process optimization ; 4&prime ; -Demethylepipodophyllotoxin ; 4-(2 ; 3 ; 5 ; 6-Tetramethylpyrazine-1)-4&prime ; -demethylepipodophyllotoxin ; Fed-batch biotransformation ; Alternaria alternata S-f6
• 刊名：Process Biochemistry
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：47
• 期：11
• 页码：1522-1531
• 全文大小：661 K

文摘

The developed tandem biotransformation process for the directional biosynthesis of a designed compound 4-(2,3,5,6-tetramethylpyrazine-1)-4¡ä-demethylepipodophyllotoxin (4-TMP-DMEP) by Alternaria alternata S-f6 was systematically optimized. 28 ¡ãC of culture temperature and 120 rpm of rotary shaker speed were suitable for the accumulation of 4-TMP-DMEP. The production (i.e., 11.1 ¡À 1.4 mg/L) of 4-TMP-DMEP was remarkably improved by using an initial yeast extract concentration of 2.5 g/L. 2.0 g/L of Span 80 was beneficial for the 4-TMP-DMEP production (i.e., 25.0 ¡À 1.5 mg/L). Furthermore, the 4-TMP-DMEP production was remarkably improved by one pulse feeding of 50 mg/L of DMEP on day 6 and two pulse feedings of 40 mg/L of TMP on days 8 and 14 when its residual level was below 50 mg/L and 10 mg/L, respectively. The 4-TMP-DMEP production of 45.1 ¡À 1.6 mg/L was obtained in the fed-batch biotransformation process, which was enhanced by 726 % and 256 % , comparing to that (i.e., 5.4 ¡À 0.4 mg/L and 0.9 mg/L/day) obtained in the batch biotransformation before optimization.