Biocatalytic Applications and Mechanistic Insights of Deoxypodophyllotoxin Synthase
-dimethoxy analogue of (+)-hydroxy-yatein indicate antarafacial C-C bond formation during the cyclization reaction and remain consistent with cation-mediated cyclization. A crystallographic study of DPS bound with vanadium(IV) oxide, succinate, and (-)-hydroxy-yatein suggests a subtle interplay of steric interactions between the substrate and the active site that can alter the course of the DPS-catalyzed reaction and thus cyclization versus hydroxylation. Finally, an efficient chemoenzymatic approach to (-)-podophyllotoxin is described that relies only on freeze-dried whole cells after DPS overexpression.
Authors
- Nian‐Qi Chen (ORCID: https://orcid.org/0000-0003-4957-5887)
- Charalambos Michael (ORCID: https://orcid.org/0000-0002-7628-114X)
- Wei‐chen Chang (ORCID: https://orcid.org/0000-0002-2341-9846)
- Mark W. Ruszczycky
- Chao-Hsuan Lin
- Wei-Yu Lin
Institutions
- North Carolina State University (US)
- Kaohsiung Medical University (TW)
- American Association of Colleges of Pharmacy (US)
- Kaohsiung Medical University Chung-Ho Memorial Hospital (TW)
- International Drug Development (FR)
- The University of Texas at Austin (US)
- I-Shou University (TW)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2026-04-07
- DOI
- https://doi.org/10.1021/jacs.6c03159
- Primary Topic
- Plant-derived Lignans Synthesis and Bioactivity
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Sun Yat-sen University
- Kaohsiung Medical University
- National Tsing Hua University
- National Science and Technology Council
- Division of Chemistry