Polyphenol curcumin, a yellow pigment, derived from the rhizomes of a plant (Curcuma longa Linn) is a natural antioxidant exhibiting a variety of pharmacological activities and therapeutic properties. It has long been used as a traditional medicine and as a preservative and coloring agent in foods. Here, curcumin-converting microorganisms were isolated from human feces, the one exhibiting the highest activity being identified as Escherichia coli. We are thus unique in discovering that E. coli was able to act on curcumin. The curcumin-converting enzyme was purified from E. coli and characterized. The native enzyme had a molecular mass of about 82 kDa and consisted of two identical subunits. The enzyme has a narrow substrate spectrum, preferentially acting on curcumin. The microbial metabolism of curcumin by the purified enzyme was found to comprise a two-step reduction, curcumin being converted NADPHdependently into an intermediate product, dihydrocurcumin, and then the end product, tetrahydrocurcumin. We named this enzyme "NADPH-dependent curcumin/dihydrocurcumin reductase" (CurA). The gene (curA) encoding this enzyme was also identified. A homology search with the BLAST program revealed that a unique enzyme involved in curcumin metabolism belongs to the mediumchain dehydrogenase/reductase superfamily. microbial screening | bioconversion S ince the dawn of civilization, natural compounds have been used as a source of medicine and foods based on their tremendous biological activities. One of the natural compounds that has been documented as having been used as a spice and a pigment since 1900 B.C. is curcumin (1). Curcumin, defined as a bis-α, β-unsaturated β-diketone (Fig. S1), has been found exclusively in the roots of Curcuma longa Linn (Zingiberaceae) (2). Curcumin has many different applications because it has a surprisingly wide variety of beneficial uses, including food coloration, cosmetics utility, and fabric dying. In addition, curcumin has a wide range of medical properties, including antitumor, antiinflammatory, antioxidant, anticancer, and analgesic uses (3). Recently, curcumin has been used in the treatment of Alzheimer's disease (4) and malaria (5), and improvement of wound healing (6). Curcumin in the diet is partially absorbed in the intestine (7). A considerable portion of the ingested curcumin reaches the cecum and colon, where a large population of indigenous bacteria exists. Although analysis of curcumin metabolism and biosynthesis would lead to the discovery of other unknown advantages of this compound, there has neither been purification of enzymes involved in the metabolic pathway for curcumin nor identification of their genes in living organisms. In addition, no information is available regarding the effect of the intestinal bacteria on curcumin metabolism.Studies on such curcumin-converting microorganisms and functional analyses of the curcumin-converting enzymes and genes would facilitate clarification of the metabolism of curcumin. In the present article, we report the isolation of cur...
