An L-threonine transaldolase is required for L- threo-β-hydroxy-α-amino acid assembly during obafluorin biosynthesis

Abstract

β-Lactone natural products occur infrequently in nature but possess a variety of potent and valuable biological activities. They are commonly derived from β-hydroxy-α-amino acids, which are themselves valuable chiral building blocks for chemical synthesis and precursors to numerous important medicines. However, despite a number of excellent synthetic methods for their asymmetric synthesis, few effective enzymatic tools exist for their preparation. Here we report cloning of the biosynthetic gene cluster for the β-lactone antibiotic obafluorin and delineate its biosynthetic pathway. We identify a nonribosomal peptide synthetase with an unusual domain architecture and an L-threonine:4-nitrophenylacetaldehyde transaldolase responsible for (2 S,3 R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoate biosynthesis. Phylogenetic analysis sheds light on the evolutionary origin of this rare enzyme family and identifies further gene clusters encoding L-threonine transaldolases. We also present preliminary data suggesting that L-threonine transaldolases might be useful for the preparation of L- threo-β-hydroxy-α-amino acids.

Abstract

Obafluorin is a β-lactone antibiotic produced by Pseudomonas fluorescens. Here the authors present the biosynthetic gene cluster and biosynthetic pathway of obafluorin, which is characterized by a central transaldolase step catalysed by a rare L-threonine transaldolase.