Regulation of intracellular formaldehyde toxicity during methanol metabolism of the methylotrophic yeast Pichia methanolica

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• 作者：Keishi Wakayama¹ ; Sakiko Yamaguchi¹ ; Akihito Takeuchi¹ ; Tasuku Mizumura² ; Shotaro Ozawa² ; Noboru Tomizuka² ; Takashi Hayakawa¹ ; Tomoyuki Nakagawa¹ ; ^{t_nakaga@gifu-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Methylotrophic yeast ; Pichia methanolica ; Formaldehyde ; Methanol metabolic enzymes ; Alcohol oxidase isozymes
• 刊名：Journal of Bioscience and Bioengineering
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：122
• 期：5
• 页码：545-549
• 全文大小：677 K

文摘

In this study we found that the methylotrophic yeast Pichia methanolica showed impaired growth on high methanol medium (>5%, or 1.56 M, methanol). In contrast, P. methanolica grew well on glucose medium containing 5% methanol, but the growth defects reappeared on glucose medium supplemented with 5 mM formaldehyde. During methanol growth of P. methanolica, formaldehyde accumulated in the medium up to 0.3 mM before it was consumed rapidly based on cell growth. These findings indicate that the growth defect of P. methanolica on high methanol media is not caused directly by methanol toxicity, but rather by formaldehyde, which is a key toxic intermediate of methanol metabolism. Moreover, during methanol growth of P. methanolica, expression of enzymes in the methanol-oxidation pathway were induced before the alcohol oxidase isozymes Mod1p and Mod2p, and Mod1p expression was induced before Mod2p. These results suggest that to avoid excess accumulation of formaldehyde—the toxic intermediate of methanol metabolism—P. methanolica grown on methanol strictly regulates the order in which methanol-metabolizing enzymes are expressed.