β-Lactone Synthetase Found in the Olefin Biosynthesis Pathway

Abstract

The first β-lactone synthetase enzyme is reported, creating an unexpected link between the biosynthesis of olefinic hydrocarbons and highly functionalized natural products. The enzyme OleC, involved in the microbial biosynthesis of long-chain olefinic hydrocarbons, reacts with syn- and anti-β-hydroxy acid substrates to yield cis- and trans-β-lactones, respectively. Protein sequence comparisons reveal that enzymes homologous to OleC are encoded in natural product gene clusters that generate β-lactone rings, suggesting a common mechanism of biosynthesis.

Active Multienzyme Assemblies for Long-Chain Olefinic Hydrocarbon Biosynthesis

“…The purification of individually expressed OleA, OleC, and OleD proteins derived from different bacteria had been reported previously (5,(7)(8)(9)(10)(11), while the purification of an OleB protein is reported here for the first time, to our knowledge. In this study, all four X. campestris Ole proteins were purified in a recombinant form from separate E. coli expression host cell lines.…”

“…Until recently, OleC was thought to catalyze the final reaction in olefin biosynthesis. However, OleC is now known to react with the product of the OleD reaction to generate a thermally labile ␤-lactone (10). The ␤-lactone undergoes spontaneous and nonbiological decarboxylation to an olefin when monitored by gas chromatography (GC), which led to the initial incorrect assignment of OleC function (10,11).…”

“…However, OleC is now known to react with the product of the OleD reaction to generate a thermally labile ␤-lactone (10). The ␤-lactone undergoes spontaneous and nonbiological decarboxylation to an olefin when monitored by gas chromatography (GC), which led to the initial incorrect assignment of OleC function (10,11). Recent data suggest that OleB acts as an unprecedented ␤-lactone decarboxylase to yield the final olefin product (10).…”

“…The ␤-lactone undergoes spontaneous and nonbiological decarboxylation to an olefin when monitored by gas chromatography (GC), which led to the initial incorrect assignment of OleC function (10,11). Recent data suggest that OleB acts as an unprecedented ␤-lactone decarboxylase to yield the final olefin product (10). Homologous gene clusters lacking an oleB gene have been identified in Streptomyces, and these produce ␤-lactone natural products rather than olefins (10).…”

“…Recent data suggest that OleB acts as an unprecedented ␤-lactone decarboxylase to yield the final olefin product (10). Homologous gene clusters lacking an oleB gene have been identified in Streptomyces, and these produce ␤-lactone natural products rather than olefins (10). Microbial secondary metabolites containing ␤-lactones often serve as antibiotics and are known as general esterase and protease inhibitors (12,13).…”