A RubisCO-like protein links SAM metabolism with isoprenoid biosynthesis

Combined omics techniques lead to the functional assignment of four enzymes involved in a new methionine salvage pathway linking polyamine metabolism with isoprenoid biosynthesis. This reaction sequence involves a homolog of nature's most abundant protein, the CO2-fixing enzyme RubisCO. Functional assignment of uncharacterized proteins is a challenge in the era of large-scale genome sequencing. Here, we combine in extracto NMR, proteomics and transcriptomics with a newly developed (knock-out) metabolomics platform to determine a potential physiological role for a ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO)-like protein from Rhodospirillum rubrum. Our studies unraveled an unexpected link in bacterial central carbon metabolism between S-adenosylmethionine–dependent polyamine metabolism and isoprenoid biosynthesis and also provide an alternative approach to assign enzyme function at the organismic level.