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

Song, Y., Guan, Z., van Merkerk, R., Pramastya, H., Abdallah, I. I., Setroikromo, R. & Quax, W. J., 15-Apr-2020, In : Journal of Agricultural and Food Chemistry. 68, 15, p. 4447-4455

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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 mg/L- 7.5 mg/L) by expressing SQS from Bacillus megaterium and eliminating bottlenecks within 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
JournalJournal of Agricultural and Food Chemistry
Issue number15
Early online date25-Mar-2020
Publication statusPublished - 15-Apr-2020

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