Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. II. Structure elucidation.
GE2270 A, produced by Planobispora rosea ATCC 53773, inhibits Gram-positive bacteria and anaerobes by acting on the bacterial protein synthesis. The structure has been determined by physico-chemical methods applied to the intact molecule and to the main hydrolysis products. Characterization by UV, IR, NMR (double quantum filter COSY), acid-base ionization, elemental analysis and FAB-MS indicated that GE2270 A is a highly modified peptide having MW 1,289 and formula C56H55N15O10S6, and a weak basic function, and that it belongs to the thiazolyl peptide group of antibiotics. Acid hydrolysis yielded a main product (MW 634), responsible for the chromophoric absorption, and a number of hydrolyzed products of lower MW. 13C NMR inverse techniques and MS studies (EI, positive ion chemical ionization, and collision induced dissociation FAB-MS-MS experiments) on GE2270 A, the chromophoric compound, and the other hydrolysis products led to the complete identification of the various amino acid residues and their sequence. Two out of the six chiral centers have been determined. The structure is thought to originate from modification of a chain of 14 amino acids in a process which creates 6 thiazole rings and one pyridine. The modification process also closes the linear polypeptide to form a cyclic part with an attached side-chain. GE2270 A plausibly has a similar biosynthetic origin to that of other thiazolyl peptide antibiotics such as nosiheptide and micrococcin.
Kettenring
J
J
MMDRI, Lepetit Research Center, Gerenzano, Varese, Italy.
Colombo
L
L
Ferrari
P
P
Tavecchia
P
P
Nebuloni
M
M
Vékey
K
K
Gallo
G G
GG
Selva
E
E
D000192:Actinomycetales / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001421:Bacteria, Anaerobic / Q000187:drug effects; D001426:Bacterial Proteins / Q000096:biosynthesis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008401:Gas Chromatography-Mass Spectrometry; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D011500:Protein Synthesis Inhibitors; D013844:Thiazoles; C068122:GE 2270 A