In vitro synthesis of new cyclodepsipeptides of the PF1022-type: probing the alpha-D-hydroxy acid tolerance of PF1022 synthetase.
The nonribosomal peptide synthetase PF1022-synthetase (PFSYN) synthesises the cyclooctadepsipeptide PF1022 from the building blocks D-lactate, D-phenyllactate and N-methylleucine. The substrate tolerance of PFSYN for hydroxy acids was probed by in vitro screening of a set of aliphatic and aromatic alpha-D-hydroxy acids with various structural modifications in the side chain. Thus, new PF1022 derivatives for example, propargyl-D-lactyl-PF1022 and beta-thienyl-D-lactyl-PF1022 were generated. The promiscuous behaviour of PFSYN towards aliphatic and aromatic alpha-D-hydroxy acids is considerably larger than that of related enniatin synthetase (ESYN) and thus gives rise to the enzymatic generation of various new PF1022 derivatives.
Müller
Jane
J
Technische Universität Berlin, Fakultät II-Institut für Chemie, Strasse des 17. Juni 124, 10629 Berlin, Germany.
Feifel
Sven C
SC
Schmiederer
Timo
T
Zocher
Rainer
R
Süssmuth
Roderich D
RD
D047630:Depsipeptides / Q000096:biosynthesis* / Q000737:chemistry*; D006880:Hydroxy Acids / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008025:Ligases / Q000378:metabolism*; D013379:Substrate Specificity
D047630:Depsipeptides; D006880:Hydroxy Acids; C075544:PF 1022A; D019344:Lactic Acid; D008025:Ligases