Total enzymatic synthesis of cis-α-irone from a simple carbon source - INSA Toulouse - Institut National des Sciences Appliquées de Toulouse Access content directly
Journal Articles Nature Communications Year : 2022

Total enzymatic synthesis of cis-α-irone from a simple carbon source


Abstract Metabolic engineering has become an attractive method for the efficient production of natural products. However, one important pre-requisite is to establish the biosynthetic pathways. Many commercially interesting molecules cannot be biosynthesized as their native biochemical pathways are not fully elucidated. Cis-α-irone, a top-end perfumery molecule, is an example. Retrobiosynthetic pathway design by employing promiscuous enzymes provides an alternative solution to this challenge. In this work, we design a synthetic pathway to produce cis-α-irone with a promiscuous methyltransferase (pMT). Using structure-guided enzyme engineering strategies, we improve pMT activity and specificity towards cis-α-irone by >10,000-fold and >1000-fold, respectively. By incorporating the optimized methyltransferase into our engineered microbial cells, ~86 mg l −1 cis-α-irone is produced from glucose in a 5 l bioreactor. Our work illustrates that integrated retrobiosynthetic pathway design and enzyme engineering can offer opportunities to expand the scope of natural molecules that can be biosynthesized.
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Dates and versions

hal-04248225 , version 1 (18-10-2023)





Xixian Chen, Rehka T, Jérémy Esque, Congqiang Zhang, Sudha Shukal, et al.. Total enzymatic synthesis of cis-α-irone from a simple carbon source. Nature Communications, 2022, 13 (1), pp.7421. ⟨10.1038/s41467-022-35232-2⟩. ⟨hal-04248225⟩
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