Biosynthesis of Rhizocticins, Antifungal Phosphonate Oligopeptides Produced by Bacillus subtilis ATCC6633

摘要

Rhizocticins are phosphonate oligopeptide antibi-otics containing the C-terminal nonproteinogenicamino acid (Z)-L-2-amino-5-phosphono-3-pentenoicacid (APPA). Here we report the identification andcharacterization of the rhizocticin biosynthetic genecluster (rhi) in Bacillus subtilis ATCC6633. RhizocticinB was heterologously produced in the nonproducerstrain Bacillus subtilis 168. A biosynthetic pathwayis proposed on the basis of bioinformatics analysisof the rhi genes. One of the steps during the biosyn-thesis of APPA is an unusual aldol reaction betweenphosphonoacetaldehyde and oxaloacetate cata-lyzed by an aldolase homolog RhiG. RecombinantRhiG was prepared, and the product of an in vitroenzymatic conversion was characterized. Access tothis intermediate allows for biochemical character-ization of subsequent steps in the pathway.