Details zur Publikation

Referenztyp Zeitschriften
DOI / URL Link
Titel (primär) Δ9-Tetrahydrocannabinolic acid synthase production in Pichia pastoris enables chemical synthesis of cannabinoids
Autor Lange, K.; Schmid, A.; Julsing, M.K.;
Journal / Serie Journal of Biotechnology
Erscheinungsjahr 2015
Department SOMA;
Band/Volume 211
Sprache englisch;
POF III (gesamt) R61;
Keywords Cannabinoids; Oxidative C–C bond formation; Two-liquid phase setup; Oxidase; Biocatalysis
UFZ Querschnittsthemen MIKAT; RU4;
Abstract Δ9-Tetrahydrocannabinol (THC) is of increasing interest as a pharmaceutical and bioactive compound. Chemical synthesis of THC uses a laborious procedure and does not satisfy the market demand. The implementation of biocatalysts for specific synthesis steps might be beneficial for making natural product availability independent from the plant. Δ9-Tetrahydrocannabinolic acid synthase (THCAS) from C. sativa L. catalyzes the cyclization of cannabigerolic acid (CBGA) to Δ9-tetrahydrocannabinolic acid (THCA), which is non-enzymatically decarboxylated to THC. We report the preparation of THCAS in amounts sufficient for the biocatalytic production of THC(A). Active THCAS was most efficiently obtained from Pichia pastoris. THCAS was produced on a 2 L bioreactor scale and the enzyme was isolated by single-step chromatography with a specific activity of 73 U g−1total protein. An organic/aqueous two-liquid phase setup for continuous substrate delivery facilitated in situ product removal. In addition, THCAS activity in aqueous environments lasted for only 20 min whereas the presence of hexane stabilized the activity over 3 h. In conclusion, production of THCAS in P. pastoris MutS KM71 KE1, subsequent isolation, and its application in a two-liquid phase setup enables the synthesis of THCA on a mg scale.
ID 16725
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=16725
Lange, K., Schmid, A., Julsing, M.K. (2015):
Δ9-Tetrahydrocannabinolic acid synthase production in Pichia pastoris enables chemical synthesis of cannabinoids
J. Biotechnol. 211 , 68 - 76