Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis
The l‐tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the “magic” mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)‐dependent decarboxylases for na...
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| Veröffentlicht in: | Chembiochem : a European journal of chemical biology 2022-12, Vol.23 (24), p.e202200551-n/a |
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| creator | Schäfer, Tim Kramer, Kristina Werten, Sebastiaan Rupp, Bernhard Hoffmeister, Dirk |
| description | The l‐tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the “magic” mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)‐dependent decarboxylases for natural product biosyntheses, PsiD is PLP‐independent and resembles type II phosphatidylserine decarboxylases. Here, we report on the in vitro biochemical characterization of Psilocybe cubensis PsiD along with in silico modeling of the PsiD structure. A non‐canonical serine protease triad for autocatalytic cleavage of the pro‐protein was predicted and experimentally verified by site‐directed mutagenesis.
How the magic begins: The l‐tryptophan decarboxylase PsiD initiates the biosynthesis of the psychotropic natural product psilocybin in Psilocybe mushrooms. Its in vitro biochemical characterization and in silico modeling of its structure identified a non‐canonical serine protease triad for autocatalytic cleavage of the proenzyme. PsiD's substrate flexibility makes it a versatile catalyst for biotechnological applications. |
| doi_str_mv | 10.1002/cbic.202200551 |
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How the magic begins: The l‐tryptophan decarboxylase PsiD initiates the biosynthesis of the psychotropic natural product psilocybin in Psilocybe mushrooms. Its in vitro biochemical characterization and in silico modeling of its structure identified a non‐canonical serine protease triad for autocatalytic cleavage of the proenzyme. PsiD's substrate flexibility makes it a versatile catalyst for biotechnological applications.</description><identifier>ISSN: 1439-4227</identifier><identifier>EISSN: 1439-7633</identifier><identifier>DOI: 10.1002/cbic.202200551</identifier><identifier>PMID: 36327140</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Biological Products ; Biosynthesis ; Carboxy-Lyases - genetics ; decarboxylases ; Depressive Disorder, Major ; enzymes ; Humans ; Mental depression ; Natural products ; Phosphatidylserine ; Psilocybin ; Pyridoxal Phosphate ; Serine proteinase ; Site-directed mutagenesis ; Tryptophan</subject><ispartof>Chembiochem : a European journal of chemical biology, 2022-12, Vol.23 (24), p.e202200551-n/a</ispartof><rights>2022 The Authors. ChemBioChem published by Wiley-VCH GmbH</rights><rights>2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4131-e913ee4c7245399911caa613f72742dee27a0e2f5a587a63d6ae137540a1d9793</citedby><cites>FETCH-LOGICAL-c4131-e913ee4c7245399911caa613f72742dee27a0e2f5a587a63d6ae137540a1d9793</cites><orcidid>0000-0002-5302-6461</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbic.202200551$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbic.202200551$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36327140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schäfer, Tim</creatorcontrib><creatorcontrib>Kramer, Kristina</creatorcontrib><creatorcontrib>Werten, Sebastiaan</creatorcontrib><creatorcontrib>Rupp, Bernhard</creatorcontrib><creatorcontrib>Hoffmeister, Dirk</creatorcontrib><title>Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis</title><title>Chembiochem : a European journal of chemical biology</title><addtitle>Chembiochem</addtitle><description>The l‐tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the “magic” mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)‐dependent decarboxylases for natural product biosyntheses, PsiD is PLP‐independent and resembles type II phosphatidylserine decarboxylases. Here, we report on the in vitro biochemical characterization of Psilocybe cubensis PsiD along with in silico modeling of the PsiD structure. A non‐canonical serine protease triad for autocatalytic cleavage of the pro‐protein was predicted and experimentally verified by site‐directed mutagenesis.
How the magic begins: The l‐tryptophan decarboxylase PsiD initiates the biosynthesis of the psychotropic natural product psilocybin in Psilocybe mushrooms. Its in vitro biochemical characterization and in silico modeling of its structure identified a non‐canonical serine protease triad for autocatalytic cleavage of the proenzyme. PsiD's substrate flexibility makes it a versatile catalyst for biotechnological applications.</description><subject>Biological Products</subject><subject>Biosynthesis</subject><subject>Carboxy-Lyases - genetics</subject><subject>decarboxylases</subject><subject>Depressive Disorder, Major</subject><subject>enzymes</subject><subject>Humans</subject><subject>Mental depression</subject><subject>Natural products</subject><subject>Phosphatidylserine</subject><subject>Psilocybin</subject><subject>Pyridoxal Phosphate</subject><subject>Serine proteinase</subject><subject>Site-directed mutagenesis</subject><subject>Tryptophan</subject><issn>1439-4227</issn><issn>1439-7633</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNqFkD1PwzAQQC0EolBYGVEk5hR_Ja5HGqBUqgQDzNHFuaiu0rjYqUr49aRqKSPT3fDunfQIuWF0xCjl96awZsQp55QmCTshF0wKHatUiNPDLjlXA3IZwpJSqlPBzslApIIrJukFmWUL8GBa9PYbWuuayFVRu8BoCi1uoYse0YAv3FdXQ8Cocj56C7Z2pitsE02sC13T48GGK3JWQR3w-jCH5OP56T17ieev01n2MI-NZILFqJlAlEZxmQitNWMGIGWiUlxJXiJyBRR5lUAyVpCKMgVkQiWSAiu10mJI7vbetXefGwxtvnQb3_Qvc95jWst0THtqtKeMdyF4rPK1tyvwXc5oviuX78rlx3L9we1BuylWWB7x31Q9oPfA1tbY_aPLs8ks-5P_ALsfeXQ</recordid><startdate>20221216</startdate><enddate>20221216</enddate><creator>Schäfer, Tim</creator><creator>Kramer, Kristina</creator><creator>Werten, Sebastiaan</creator><creator>Rupp, Bernhard</creator><creator>Hoffmeister, Dirk</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-5302-6461</orcidid></search><sort><creationdate>20221216</creationdate><title>Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis</title><author>Schäfer, Tim ; Kramer, Kristina ; Werten, Sebastiaan ; Rupp, Bernhard ; Hoffmeister, Dirk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4131-e913ee4c7245399911caa613f72742dee27a0e2f5a587a63d6ae137540a1d9793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biological Products</topic><topic>Biosynthesis</topic><topic>Carboxy-Lyases - genetics</topic><topic>decarboxylases</topic><topic>Depressive Disorder, Major</topic><topic>enzymes</topic><topic>Humans</topic><topic>Mental depression</topic><topic>Natural products</topic><topic>Phosphatidylserine</topic><topic>Psilocybin</topic><topic>Pyridoxal Phosphate</topic><topic>Serine proteinase</topic><topic>Site-directed mutagenesis</topic><topic>Tryptophan</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schäfer, Tim</creatorcontrib><creatorcontrib>Kramer, Kristina</creatorcontrib><creatorcontrib>Werten, Sebastiaan</creatorcontrib><creatorcontrib>Rupp, Bernhard</creatorcontrib><creatorcontrib>Hoffmeister, Dirk</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Chembiochem : a European journal of chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schäfer, Tim</au><au>Kramer, Kristina</au><au>Werten, Sebastiaan</au><au>Rupp, Bernhard</au><au>Hoffmeister, Dirk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis</atitle><jtitle>Chembiochem : a European journal of chemical biology</jtitle><addtitle>Chembiochem</addtitle><date>2022-12-16</date><risdate>2022</risdate><volume>23</volume><issue>24</issue><spage>e202200551</spage><epage>n/a</epage><pages>e202200551-n/a</pages><issn>1439-4227</issn><eissn>1439-7633</eissn><abstract>The l‐tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the “magic” mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)‐dependent decarboxylases for natural product biosyntheses, PsiD is PLP‐independent and resembles type II phosphatidylserine decarboxylases. Here, we report on the in vitro biochemical characterization of Psilocybe cubensis PsiD along with in silico modeling of the PsiD structure. A non‐canonical serine protease triad for autocatalytic cleavage of the pro‐protein was predicted and experimentally verified by site‐directed mutagenesis.
How the magic begins: The l‐tryptophan decarboxylase PsiD initiates the biosynthesis of the psychotropic natural product psilocybin in Psilocybe mushrooms. Its in vitro biochemical characterization and in silico modeling of its structure identified a non‐canonical serine protease triad for autocatalytic cleavage of the proenzyme. PsiD's substrate flexibility makes it a versatile catalyst for biotechnological applications.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36327140</pmid><doi>10.1002/cbic.202200551</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-5302-6461</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biological Products Biosynthesis Carboxy-Lyases - genetics decarboxylases Depressive Disorder, Major enzymes Humans Mental depression Natural products Phosphatidylserine Psilocybin Pyridoxal Phosphate Serine proteinase Site-directed mutagenesis Tryptophan |
| title | Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis |
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