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The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
Pantothenate synthetase from Escherichia coli (PS E. coli ) catalyzes the ATP-dependent condensation of ( R )-pantoic acid and β-alanine to yield ( R )-pantothenic acid (vitamin B 5 ), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the en...
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| Published in: | Organic & biomolecular chemistry 2021-05, Vol.19 (2), p.4515-4519 |
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| cites | cdi_FETCH-LOGICAL-c428t-9c0cd9d5bc05ce1b12ac49072c9aca5f7e88fc5dbca1a25f60d7e9c97a6a43c33 |
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| container_title | Organic & biomolecular chemistry |
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| creator | Abidin, Mohammad Z Saravanan, Thangavelu Strauss, Erick Poelarends, Gerrit J |
| description | Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) catalyzes the ATP-dependent condensation of (
R
)-pantoic acid and β-alanine to yield (
R
)-pantothenic acid (vitamin B
5
), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (
R
)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PS
E. coli
enabled the efficient synthesis of pharmaceutically-relevant vitamin B
5
antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.
Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) has a broad substrate scope, accepting diverse amines in the amidation of (
R
)-pantoate, enabling the facile synthesis of pharmaceutically relevant vitamin B5 antimetabolites. |
| doi_str_mv | 10.1039/d1ob00238d |
| format | article |
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Escherichia coli
(PS
E. coli
) catalyzes the ATP-dependent condensation of (
R
)-pantoic acid and β-alanine to yield (
R
)-pantothenic acid (vitamin B
5
), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (
R
)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PS
E. coli
enabled the efficient synthesis of pharmaceutically-relevant vitamin B
5
antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.
Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) has a broad substrate scope, accepting diverse amines in the amidation of (
R
)-pantoate, enabling the facile synthesis of pharmaceutically relevant vitamin B5 antimetabolites.</description><identifier>ISSN: 1477-0520</identifier><identifier>ISSN: 1477-0539</identifier><identifier>EISSN: 1477-0539</identifier><identifier>DOI: 10.1039/d1ob00238d</identifier><identifier>PMID: 33913984</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Acids ; Alanine ; Amides ; Amides - chemical synthesis ; Amides - chemistry ; Amines ; Amines - chemistry ; Antimetabolites ; Antimicrobial agents ; Biocatalysis ; Biosynthesis ; Carboxylic acids ; Chemistry ; Coenzyme A ; Condensates ; E coli ; Escherichia coli - enzymology ; Molecular Structure ; NMR ; Nuclear magnetic resonance ; Pantoic acid ; Pantothenic acid ; Pantothenic Acid - analogs & derivatives ; Pantothenic Acid - chemical synthesis ; Pantothenic Acid - chemistry ; Pantothenic Acid - metabolism ; Pantothenic Acid - pharmacology ; Peptide Synthases - metabolism ; Substrates ; Tryptamine ; Tryptamines</subject><ispartof>Organic & biomolecular chemistry, 2021-05, Vol.19 (2), p.4515-4519</ispartof><rights>Copyright Royal Society of Chemistry 2021</rights><rights>This journal is © The Royal Society of Chemistry 2021 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-9c0cd9d5bc05ce1b12ac49072c9aca5f7e88fc5dbca1a25f60d7e9c97a6a43c33</citedby><cites>FETCH-LOGICAL-c428t-9c0cd9d5bc05ce1b12ac49072c9aca5f7e88fc5dbca1a25f60d7e9c97a6a43c33</cites><orcidid>0000-0002-6917-6368 ; 0000-0002-1966-833X ; 0000-0002-0792-9811 ; 0000-0002-9898-8226</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33913984$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abidin, Mohammad Z</creatorcontrib><creatorcontrib>Saravanan, Thangavelu</creatorcontrib><creatorcontrib>Strauss, Erick</creatorcontrib><creatorcontrib>Poelarends, Gerrit J</creatorcontrib><title>The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides</title><title>Organic & biomolecular chemistry</title><addtitle>Org Biomol Chem</addtitle><description>Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) catalyzes the ATP-dependent condensation of (
R
)-pantoic acid and β-alanine to yield (
R
)-pantothenic acid (vitamin B
5
), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (
R
)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PS
E. coli
enabled the efficient synthesis of pharmaceutically-relevant vitamin B
5
antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.
Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) has a broad substrate scope, accepting diverse amines in the amidation of (
R
)-pantoate, enabling the facile synthesis of pharmaceutically relevant vitamin B5 antimetabolites.</description><subject>Acids</subject><subject>Alanine</subject><subject>Amides</subject><subject>Amides - chemical synthesis</subject><subject>Amides - chemistry</subject><subject>Amines</subject><subject>Amines - chemistry</subject><subject>Antimetabolites</subject><subject>Antimicrobial agents</subject><subject>Biocatalysis</subject><subject>Biosynthesis</subject><subject>Carboxylic acids</subject><subject>Chemistry</subject><subject>Coenzyme A</subject><subject>Condensates</subject><subject>E coli</subject><subject>Escherichia coli - enzymology</subject><subject>Molecular Structure</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Pantoic acid</subject><subject>Pantothenic acid</subject><subject>Pantothenic Acid - analogs & derivatives</subject><subject>Pantothenic Acid - chemical synthesis</subject><subject>Pantothenic Acid - chemistry</subject><subject>Pantothenic Acid - metabolism</subject><subject>Pantothenic Acid - pharmacology</subject><subject>Peptide Synthases - metabolism</subject><subject>Substrates</subject><subject>Tryptamine</subject><subject>Tryptamines</subject><issn>1477-0520</issn><issn>1477-0539</issn><issn>1477-0539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpdkstLxDAQxoMovi_elYIXEVaTpq9cBN8Kghc9h-lk6nZpmzVpF_a_N7rr-jhl8s0vHzN8YexA8DPBpTo3wpacx7Iwa2xbJHk-4qlU66s65ltsx_sJ50LlWbLJtqRUQqoi2WaTlzFFpbNgImjrjiKPdkqRraIpdL3tx9RBH9R5F8oePEVBKBvyUbgvZV_7rwdjcC0gDX2N0DTzyFFDs-Dy6WzI77GNChpP-8tzl73e3b5cP4yenu8fry-fRpjERT9SyNEok5bIUyRRihgwUTyPUQFCWuVUFBWmpkQQEKdVxk1OClUOGSQSpdxlFwvf6VC2ZJC63kGjp65uwc21hVr_7XT1WL_ZmS5EyrNcBIOTpYGz7wP5Xre1R2oa6MgOXsepUIUQcVIE9PgfOrGD68J6gZIBy5RSgTpdUOis946q1TCC688I9Y14vvqK8CbAR7_HX6HfmQXgcAE4j6vuzx-QHyAqpDU</recordid><startdate>20210526</startdate><enddate>20210526</enddate><creator>Abidin, Mohammad Z</creator><creator>Saravanan, Thangavelu</creator><creator>Strauss, Erick</creator><creator>Poelarends, Gerrit J</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><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>7QO</scope><scope>7T7</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6917-6368</orcidid><orcidid>https://orcid.org/0000-0002-1966-833X</orcidid><orcidid>https://orcid.org/0000-0002-0792-9811</orcidid><orcidid>https://orcid.org/0000-0002-9898-8226</orcidid></search><sort><creationdate>20210526</creationdate><title>The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides</title><author>Abidin, Mohammad Z ; Saravanan, Thangavelu ; Strauss, Erick ; Poelarends, Gerrit J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-9c0cd9d5bc05ce1b12ac49072c9aca5f7e88fc5dbca1a25f60d7e9c97a6a43c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acids</topic><topic>Alanine</topic><topic>Amides</topic><topic>Amides - chemical synthesis</topic><topic>Amides - chemistry</topic><topic>Amines</topic><topic>Amines - chemistry</topic><topic>Antimetabolites</topic><topic>Antimicrobial agents</topic><topic>Biocatalysis</topic><topic>Biosynthesis</topic><topic>Carboxylic acids</topic><topic>Chemistry</topic><topic>Coenzyme A</topic><topic>Condensates</topic><topic>E coli</topic><topic>Escherichia coli - enzymology</topic><topic>Molecular Structure</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Pantoic acid</topic><topic>Pantothenic acid</topic><topic>Pantothenic Acid - analogs & derivatives</topic><topic>Pantothenic Acid - chemical synthesis</topic><topic>Pantothenic Acid - chemistry</topic><topic>Pantothenic Acid - metabolism</topic><topic>Pantothenic Acid - pharmacology</topic><topic>Peptide Synthases - metabolism</topic><topic>Substrates</topic><topic>Tryptamine</topic><topic>Tryptamines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abidin, Mohammad Z</creatorcontrib><creatorcontrib>Saravanan, Thangavelu</creatorcontrib><creatorcontrib>Strauss, Erick</creatorcontrib><creatorcontrib>Poelarends, Gerrit J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Organic & biomolecular chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abidin, Mohammad Z</au><au>Saravanan, Thangavelu</au><au>Strauss, Erick</au><au>Poelarends, Gerrit J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides</atitle><jtitle>Organic & biomolecular chemistry</jtitle><addtitle>Org Biomol Chem</addtitle><date>2021-05-26</date><risdate>2021</risdate><volume>19</volume><issue>2</issue><spage>4515</spage><epage>4519</epage><pages>4515-4519</pages><issn>1477-0520</issn><issn>1477-0539</issn><eissn>1477-0539</eissn><abstract>Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) catalyzes the ATP-dependent condensation of (
R
)-pantoic acid and β-alanine to yield (
R
)-pantothenic acid (vitamin B
5
), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (
R
)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PS
E. coli
enabled the efficient synthesis of pharmaceutically-relevant vitamin B
5
antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.
Pantothenate synthetase from
Escherichia coli
(PS
E. coli
) has a broad substrate scope, accepting diverse amines in the amidation of (
R
)-pantoate, enabling the facile synthesis of pharmaceutically relevant vitamin B5 antimetabolites.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>33913984</pmid><doi>10.1039/d1ob00238d</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-6917-6368</orcidid><orcidid>https://orcid.org/0000-0002-1966-833X</orcidid><orcidid>https://orcid.org/0000-0002-0792-9811</orcidid><orcidid>https://orcid.org/0000-0002-9898-8226</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1477-0520 |
| ispartof | Organic & biomolecular chemistry, 2021-05, Vol.19 (2), p.4515-4519 |
| issn | 1477-0520 1477-0539 1477-0539 |
| language | eng |
| recordid | cdi_proquest_journals_2531986999 |
| source | Royal Society of Chemistry |
| subjects | Acids Alanine Amides Amides - chemical synthesis Amides - chemistry Amines Amines - chemistry Antimetabolites Antimicrobial agents Biocatalysis Biosynthesis Carboxylic acids Chemistry Coenzyme A Condensates E coli Escherichia coli - enzymology Molecular Structure NMR Nuclear magnetic resonance Pantoic acid Pantothenic acid Pantothenic Acid - analogs & derivatives Pantothenic Acid - chemical synthesis Pantothenic Acid - chemistry Pantothenic Acid - metabolism Pantothenic Acid - pharmacology Peptide Synthases - metabolism Substrates Tryptamine Tryptamines |
| title | The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides |
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