Work

Engineered Production of Strictosidine and Analogues in Yeast

Year: 2022

Type: article

Abstract: Monoterpene indole alkaloids (MIAs) are an expansive class of plant natural products, many of which have been named on the World Health Organization's List of Essential Medicines. Low production from native plant hosts necessitates a more reliable source of these drugs to meet global demand. Here, we report the development of a yeast-based platform for high-titer production of the universal MIA precursor, strictosidine. Our fed-batch platform produces ∼50 mg/L strictosidine, starting from the commodity chemicals geraniol and tryptamine. The microbially produced strictosidine was purified to homogeneity and characterized by NMR. Additionally, our approach enables the production of halogenated strictosidine analogues through the feeding of modified tryptamines. The MIA platform strain enables rapid access to strictosidine for reconstitution and production of downstream MIA natural products.

Source: ACS Synthetic Biology

DOI: 10.1021/acssynbio.2c00037

Authors: Joshua Misa, John M. Billingsley, Kanji Niwa, Rachel K. Yu, Yi Tang

Institution: University of California, Los Angeles

Language: English

Topic: Microbial Metabolic Engineering and Bioproduction

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institute of General Medical Sciences, Division of Materials Research, National Center for Complementary and Integrative Health

Awards: G494560991, G5368402356, Chemistry Biology Interface Training Program, G718364985