Biosynthesis of the lantibiotic Pep5. Isolation and characterization of a prepeptide containing dehydroamino acids

Content Provider	Scilit
Author	Weil, Hans-Peter Beck-Sickinger, Annette G. Metzger, Jorg Stevanovic, Stefan Jung, Gunther Josten, Michaele Sahl, Hans-Georg
Copyright Year	1990
Description	Journal: Journal of Biological Inorganic Chemistry Pep5 is a tricyclic peptide antibiotic which contains the unusual amino acids dehydrobutyrine, lanthionine and 3-methyllanthionine. It is matured from a 60-amino-acid precursor peptide (pre-Pep5) deduced from the sequence of the structural gene pepA. To study the biosynthesis of Pep5 we tried to isolate the primary translation product. We identified a peptide in crude extracts of the Pep5-producing Staphylococcus epidermidis strain using antibodies raised against a synthetic 26-residue peptide representing the leader peptide region of pre-Pep5. The putative precursor was purified by reversed-phase HPLC. The isolated peptide did not react with antibodies directed against a C-terminal fragment of mature Pep5 containing two sulfide bridges. Neither lanthionine nor 3-methyllanthionine was detected in amino acid analysis of the isolated precursor. Its amino acid sequence was identical with the sequence predicted from pepA, but Edman degradation stopped at the first threonine residue of the prolantibiotic region indicating a posttranslational modification at this position. The molecular mass of the isolated peptide was 6575.4 +/- 1.7 Da, determined by ion-spray mass spectrometry. This is in agreement with a molecule being dehydrated at the four threonine and the two serine residues in the propeptide region; such a peptide has a calculated molecular mass of 6576.7 Da. The results strongly suggest that maturation of the lantibiotic Pep5 is initiated by selective dehydration of hydroxyamino acids in the propeptide region of the primary translation product and that thioether ring formation is not closely linked to dehydration.
Ending Page	223
Starting Page	217
ISSN	2573508X
e-ISSN	14321327
DOI	10.1111/j.1432-1033.1990.tb19446.x
Journal	Journal of Biological Inorganic Chemistry
Issue Number	1
Volume Number	194
Language	English
Publisher	Wiley-Blackwell
Publisher Date	1990-11-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Inorganic Chemistry Analytical Chemistry Primary Translation Product Lantibiotic Pep5
Content Type	Text
Resource Type	Article
Subject	Biochemistry Inorganic Chemistry