Production of squalene in Bacillus subtilis by squalene synthases screening and metabolic engineering

Yafeng Song, Zheng Guan, Ronald van Merkerk, Hegar Pramastya, Ingy I Abdallah, Rita Setroikromo, Wim J Quax*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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Squalene synthase (SQS) catalyzes the conversion of two farnesyl pyrophosphates to squalene, an important intermediate in between isoprene and valuable triterpenoids. In this study, we have constructed a novel biosynthesis pathway for squalene in Bacillus subtilis and performed metabolic engineering aiming at facilitating further exploitation and production of squalene-derived triterpenoids. Therefore, systematic studies and analysis were performed including selection of multiple SQS candidates from various organisms, comparison of expression vectors, optimization of cultivation temperatures, and examination of rate-limiting factors within the synthetic pathway. We were, for the first time, able to obtain squalene synthesis in B. subtilis. Furthermore, we achieved a 29-fold increase of squalene yield (0.26-7.5 mg/L) by expressing SQS from Bacillus megaterium and eliminating bottlenecks within the upstream methylerythritol-phosphate pathway. Moreover, our findings showed that also ispA could positively affect the production of squalene.

Original languageEnglish
Pages (from-to)4447-4455
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Issue number15
Early online date25-Mar-2020
Publication statusPublished - 15-Apr-2020

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