角鲨烯
角鲨烯单加氧酶
麦角甾醇
酵母
生物化学
酿酒酵母
酶
化学
生物
生物合成
作者
Masahiro Tominaga,Kôji Miyazaki,Shoko Hataya,Yuichi Mitsui,S. Kuroda,Akihiko Kondo,Jun Ishii
标识
DOI:10.1016/j.jbiosc.2022.04.004
摘要
Fermentative production of squalene in yeast as an alternative approach to extracting squalene from sharks or plants has attracted significant interest. However, squalene accumulation is limited due to its inevitable high-flux allocation toward ergosterol synthesis. In this study, we described expression control of squalene monooxygenase (Erg1p), the first-step enzyme of ergosterol synthesis from squalene, to significantly reduce squalene loss. We replaced the ERG1 promoter (PERG1) with three natural yeast promoters with different activities (PPCL2, PHCM1, and PTHI2). ERG1 controlled by PTHI2 showed 20 times higher squalene production compared with the wild-type strain, whereas the other two strains exhibited no significant difference. By combining the overexpression of rate-limiting enzyme and the deletion of non-essential competing pathway gene, the yeast Saccharomyces cerevisiae produced up to 379 mg/L of squalene.
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