Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the key catalyst of CO2 fixation in nature. RuBisCO forms I, II, and III catalyze CO2 fixation reactions, whereas form IV, also called the RuBisCO-like protein (RLP), is known to have no carboxylase or oxygenase activities. Here, we describe an RLP in Ochrobactrum anthropi ATCC 49188 (Oant_3067; HamA) that functions as an oxygenase in the metabolism of D-hamamelose, a branched-chain hexose found in most higher plants. The D-hamamelose pathway is comprised of five previously unknown enzymes: D-hamamelose dehydrogenase, D-hamamelono-lactonase, D-hamamelonate kinase, D-hamamelonate-2′,5-bisphosphate dehydrogenase (decarboxylating), and the RLP 3-keto-D-ribitol-1,5-bisphosphate (KRBP) oxygenase, which converts KRBP to 3-D-phosphoglycerate and phosphoglycolate. HamA represents the first RLP catalyzing the O2-dependent oxidative C-C bond cleavage reaction, and our findings may provide insights into its applications in oxidative cleavage of organic molecules. [ABSTRACT FROM AUTHOR]