Autor: |
Lukas Ernst, Hui Lyu, Pi Liu, Christian Paetz, Hesham M. B. Sayed, Tomke Meents, Hongwu Ma, Ludger Beerhues, Islam El-Awaad, Benye Liu |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
|
Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-024-48879-w |
Popis: |
Abstract Medicinal compounds from plants include bicyclo[3.3.1]nonane derivatives, the majority of which are polycyclic polyprenylated acylphloroglucinols (PPAPs). Prototype molecules are hyperforin, the antidepressant constituent of St. John’s wort, and garcinol, a potential anticancer compound. Their complex structures have inspired innovative chemical syntheses, however, their biosynthesis in plants is still enigmatic. PPAPs are divided into two subclasses, named type A and B. Here we identify both types in Hypericum sampsonii plants and isolate two enzymes that regiodivergently convert a common precursor to pivotal type A and B products. Molecular modelling and substrate docking studies reveal inverted substrate binding modes in the two active site cavities. We identify amino acids that stabilize these alternative binding scenarios and use reciprocal mutagenesis to interconvert the enzymatic activities. Our studies elucidate the unique biochemistry that yields type A and B bicyclo[3.3.1]nonane cores in plants, thereby providing key building blocks for biotechnological efforts to sustainably produce these complex compounds for preclinical development. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|