Cyclopeptin und Dehydrocyclopeptin

• Joachim Framm

• Lutz Nover

• Aida El Azzouny

• Heinrich Richter

• Klaus Winter

• Sabine Werner

• Martin Luckner

書誌事項

タイトル別名

• Zwischenprodukte der Biosynthese von Alkaloiden der Cyclopenin‐Viridicatin‐Gruppe bei <i>Penicillium cyclopium</i> Westling

抄録

Feeding tritium labeled N ‐methyl phenylalanine and a number of N ‐methylated and unmethylated cyclic and acyclic anthranilic‐acid‐phenylalanine‐peptides, the biosynthesis of the benzodiazepine alkaloids cyclopenin and cyclopenol by Penicillium cyclopium was investigated. The results show that only the two N‐methylated cyclic peptides, cyclo‐(An‐MePhe) and 3,10‐dehydro‐cyclo‐(An‐MePhe) were incorporated without degradation and marked depression of the incorporation rate by non‐radioactive phenylalanine. The negative results with the acyclic dipeptides, N ‐methylphenylalanine and cyclo‐(An‐Phe), some of which should be intermediates in the biosynthesis of cyclo‐(An‐MePhe), indicate that the formation of the latter proceeds via enzyme bound intermediates as it was found also for more complex cyclic peptide derivatives like gramicidine S. Aside the formation of the peptide bonds, the N‐methylation seems to be part of the reaction sequence on this enzyme complex, too. By looking for cyclo‐(An‐MePhe) and its dehydroderivative in cultures of P. cyclopium , two hitherto unknown benzodiazepine derivatives were isolated. Their structures were elucidated by physico‐chemical methods and comparison with synthetic material. The compounds were called cyclopeptine and dehydrocyclopeptine and identified as cyclo‐[anthranoyl‐( S )‐ N ‐methyl phenylalanyl] and 3,10‐trans‐dehydro‐cyclo‐[anthranoyl‐ N ‐methyl phenylalanyl] respectively. m ‐Hydroxylated derivatives of both substances, the structure of which would correspond to that of cyclopend were not detectable. The biosyntheses of cyclopeptine and dehydrocyclopeptine from phenylalanine and the coordinated formation of both compounds together with cyclopenin and cyclopenol during the mould's idiophase further prove that they are true intermediates in the synthesis of benzodiazepine alkaloids in P. cyclopium . Cyclopeptine can be reversibly transformed into dehydrocyclopeptine. According to these and former experimental results the biosynthesis of the benzodiazepine and quinoline alkaloids of P. cyclopium seems to proceed in the following manner: The precursor amino acids ( S )‐phenylalanine and anthranilic acid together with the methylgroup of methionine form an enzyme bound acyclic dipeptide intermediate (presumably an anthranoyl‐( S )‐ N ‐methyl phenylalanyl thioester) which undergoes cyclization to the benzodiazepin derivatives to release cyclopeptin from the enzyme. Cyclopeptin with NAD as hydrogen acceptor forms dehydrocyclopeptin in the presence of cyclopeptine dehydrogenase. Dehydrocyclopeptine by an epoxydation requiring molecular oxygen is transformed to cyclopenin, which upon m ‐hydroxylation yields cyclopenol. Both, cyclopenin and cyclopenol, in the conidiospores are converted by cyclopenase to the quinoline derivatives, viridicatin and viridicatol.

収録刊行物

• European Journal of Biochemistry

  European Journal of Biochemistry 37 (1), 78-85, 1973-08

  Wiley

キーワード

• Biochemistry

詳細情報

• CRID: 1364233270297861632
• NII論文ID: 30014362434
• DOI: 10.1111/j.1432-1033.1973.tb02959.x
• ISSN: 14321033
• ISSN: 00142956
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1432-1033.1973.tb02959.x
• Web Site: https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1973.tb02959.x
• データソース種別:
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  • CiNii Articles