Directed biosynthesis of new enniatins.
New cyclohexadepsipeptides of the enniatin type with potential anthelmintic properties were produced by two different strategies: 1. In vitro synthesis by use of the multienzyme enniatin synthetase, and 2. in vivo precursor feeding of enniatin producing strains Fusarium scirpi and Fusarium sambucinum. The compounds were analyzed by HPLC, various NMR measurements and mass spectrometry. The three N-methyl L-amino acid positions in the enniatin B molecule could be gradually replaced by other (N-methyl) L-amino acids, e.g. alanine, cysteine, threonine and serine. The latter two amino acids yield new enniatins with functional groups in the hydrophobic side chains. Similarly the three D-2-hydroxyisovalerate residues, present in all naturally occuring enniatins, could be substituted by D-2-hydroxybutyric acid and D-lactic acid. Despite its lower yield the in vitro synthesis has the advantage of a broader variety of products formed.
Krause
M
M
Chemisches Institut der Fakultät II, Fachrichtung Biochemie und Molekulare Biologie, Technische Universität Berlin, Germany.
Lindemann
A
A
Glinski
M
M
Hornbogen
T
T
Bonse
G
G
Jeschke
P
P
Thielking
G
G
Gau
W
W
Kleinkauf
H
H
Zocher
R
R
D000871:Anthelmintics / Q000737:chemistry / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003470:Culture Media; D047630:Depsipeptides; D005656:Fungal Proteins / Q000096:biosynthesis; D005670:Fusarium / Q000201:enzymology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010453:Peptide Synthases / Q000378:metabolism; D010455:Peptides
D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D003470:Culture Media; D047630:Depsipeptides; D005656:Fungal Proteins; D010455:Peptides; C100264:enniatins; D010453:Peptide Synthases; C023122:enniatin B synthetase