Department Pharmaceutical Microbiology at the Hans Knöll Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745, Jena, Germany.
Angew Chem Int Ed Engl. 2017 Sep 25;56(40):12352-12355. doi: 10.1002/anie.201705489. Epub 2017 Aug 25.
Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called "magic mushrooms". Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes, namely i) PsiD, which represents a new class of fungal l-tryptophan decarboxylases, ii) PsiK, which catalyzes the phosphotransfer step, iii) the methyltransferase PsiM, catalyzing iterative N-methyl transfer as the terminal biosynthetic step, and iv) PsiH, a monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step-economic route from 4-hydroxy-l-tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.
裸盖菇素是一种精神活性色胺衍生的天然产物，来源于具有致幻作用的裸盖菇属真菌的菌盖，即所谓的“神奇蘑菇”。尽管其结构已经为人所知 60 年，但它的生物合成的酶学基础仍然不清楚。我们鉴定了四种裸盖菇素生物合成酶，分别是：i）PsiD，它代表了一类新型真菌 l-色氨酸脱羧酶；ii）PsiK，它催化磷酸转移步骤；iii）甲基转移酶 PsiM，催化作为终末生物合成步骤的迭代 N-甲基转移；iv）PsiH，一种单加氧酶。在 PsiD/PsiK/PsiM 的联合反应中，从 4-羟基-l-色氨酸以经济有效的一步法酶促合成了裸盖菇素。鉴于人们对裸盖菇素重新产生了药物学兴趣，我们的结果可能为其生物技术生产奠定了基础。
