Nanoscale control of the polymerization of silicon and oxygen determines the structures and properties of a wide range of siloxane-based materials, including glasses, ceramics, mesoporous molecular sieves and catalysts, elastomers, resins, insulators, optical coatings, and photoluminescent polymers. In contrast to anthropogenic and geological syntheses of these materials that require extremes of temperature, pressure, or pH, living systems produce a remarkable diversity of nanostructured silicates at ambient temperatures and pressures and at near-neutral pH. We show here that the protein filaments and their constituent subunits comprising the axial cores of silica spicules in a marine sponge chemically and spatially direct the polymerization of silica and silicone polymer networks from the corresponding alkoxide substrates in vitro, under conditions in which such syntheses otherwise require either an acid or base catalyst. Homology of the principal protein to the well known enzyme cathepsin L points to a possible reaction mechanism that is supported by recent site-directed mutagenesis experiments. The catalytic activity of the ''silicatein'' (silica protein) molecule suggests new routes to the synthesis of silicon-based materials.Silicon, the second most abundant element in the earth's crust, interacts with living systems by mechanisms that have remained poorly understood (1-6). Evidence suggests that silicon is essential for normal growth and biological function in a diversity of plant, animal, and microbial systems (2); silicon compounds have been shown to modulate these activities (1, 2), but the molecular mechanisms of these effects have proved elusive. Studies of marine organisms that produce relatively large masses of silicified structures (3) show the underlying molecular and genetic mechanisms by which living systems process silicon. Hildebrand et al. (7) recently characterized the cDNAs coding for a family of silicon transporters in diatoms and showed that the transporters are likely transmembrane proteins. We have found that the marine sponge Tethya aurantia produces copious silica spicules (1-2 mm in length and 30 m in diameter) that constitute 75% of the dry weight of the organism and that each of these spicules contains a central axial filament of protein (1-2 mm in length and 2 m in diameter) consisting of three very similar subunits that we have named silicateins (for silica proteins; ref. 8). Characterization of silicatein ␣ (the subunit comprising nearly 70% of the mass of the filaments) and its cloned cDNA indicated that it is homologous to members of the cathepsin L subfamily of the papain family of proteolytic enzymes (8).We show here that, at neutral pH, the silicatein filaments and their constituent subunits catalyze the in vitro polymerization of silica and silsesquioxanes from tetraethoxysilane and organically modified silicon triethoxides, respectively. These substrates were chosen because of their stability at neutral pH and the similarity of their chemical reactivity to that of...