Department Pharmaceutical Microbiology at the Hans Knöll Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745, Jena, Germany.
The Usona Institute, 2800 Woods Hollow Road, Madison, WI, 53711, USA.
Chembiochem. 2019 Nov 18;20(22):2824-2829. doi: 10.1002/cbic.201900358. Epub 2019 Oct 17.
Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6-methylated psilocybin and baeocystin from 4-hydroxy-6-methyl-l-tryptophan, which was decarboxylated and phosphorylated by the Psilocybe cubensis biosynthesis enzymes PsiD and PsiK. N-Methylation was catalyzed by PsiM. We further present an in silico structural model of PsiM that revealed a well-conserved SAM-binding core along with peripheral nonconserved elements that likely govern substrate preferences.
裸盖菇素及其直接前体裸头草碱是具有致幻作用的裸盖菇属蕈类中的吲哚生物碱。目前，人们对裸盖菇素作为治疗抑郁症和焦虑症的一种选择的药物治疗的兴趣正在进行深入的临床试验研究。在这里，我们报告了一种生物催化途径，可从 4-羟基-6-甲基-l-色氨酸合成 6-甲基裸盖菇素和裸头草碱，该途径由 Psilocybe cubensis 生物合成酶 PsiD 和 PsiK 进行脱羧和磷酸化。N-甲基化由 PsiM 催化。我们进一步提出了 PsiM 的计算机结构模型，该模型揭示了一个保守的 SAM 结合核心，以及可能控制底物偏好的外围非保守元素。
