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

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Total enzymatic synthesis of cis-α-irone from a simple carbon source
Title:
Total enzymatic synthesis of cis-α-irone from a simple carbon source
Journal Title:
Nature Communications
Publication Date:
02 December 2022
Citation:
Chen, X., T, R., Esque, J., Zhang, C., Shukal, S., Lim, C. C., Ong, L., Smith, D., & André, I. (2022). Total enzymatic synthesis of cis-α-irone from a simple carbon source. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-35232-2
Abstract:
AbstractMetabolic 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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the A*STAR - Industry Alignment Fund - Pre-Positioning Programme (IAF-PP)
Grant Reference no. : H20H6a0028

This research / project is supported by the A*STAR - AME Young Individual Research Grants
Grant Reference no. : A1984c0040

This research / project is supported by the A*STAR - AME Young Individual Research Grants
Grant Reference no. : A2084c0064
Description:
ISSN:
2041-1723
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