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Penicillin biosynthesis: intermediates of biosynthesis of δ‐ l ‐α‐aminoadipyl‐ l ‐cysteinyl‐ d ‐valine formed by ACV synthetase from Acremonium chrysogenum
Author(s) -
Kallow Wibke,
Neuhof Torsten,
Arezi Bahram,
Jungblut Peter,
von Döhren Hans
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00977-0
Subject(s) - chemistry , biosynthesis , valine , tripeptide , stereochemistry , performic acid , biochemistry , cysteic acid , cysteine , nonribosomal peptide , enzyme , peptide , amino acid , cystine
The tripeptide δ‐ l ‐α‐aminoadipyl‐ l ‐cysteinyl‐ d ‐valine (LLD‐ACV) is synthesised by the multifunctional enzyme ACV synthetase integrating four steps of the penicillin and cephalosporin biosynthetic pathway. Peptide synthesis follows the thiotemplate mechanism from intermediates bound as thioesters to the enzyme. The formation of δ‐( l ‐α‐aminoadipyl)‐ l ‐cysteinyl‐thioester in the absence of l ‐valine was shown by isolation of the enzyme–substrate complex and cleavage of the covalently bound intermediate with performic acid. The dipeptide was recovered as cysteic acid or cysteic acid oxime and detected by HPLC and MALDI‐TOF mass spectrometry. We conclude that the first peptide bond is formed between δ‐carboxyl of l ‐aminoadipic acid and l ‐cysteine, followed by addition of the dipeptidyl intermediate to l ‐valine.