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Drug delivery inspired by spiky sponges

van der Walle, C.F. (2008) Drug delivery inspired by spiky sponges. Journal of Pharmacy and Pharmacology, 60 (S1). A65-A65. ISSN 0022-3573

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Silica materials are of interest in biotechnology and drug delivery (Giri et al 2007) but controllable silicate formation is very difficult. Yet a variety of sponge species make highly ordered specific glass structures called spicules (Shimizu et al 1998). Harnessing the processes that underlie this biosynthesis has considerable application. The enzyme silicatein forms part of the organic filament found in spicules, which condenses silicate in situ. Both wild-type and recombinant silicatein have been shown to catalyse the condensation of siloxanes such as tetraethoxysilane (Cha et al 1999). However, neither the wild-type nor recombinant silicatein are amenable to biophysical study due to low levels of protein expression and inclusion body formation when recombinantly expressed in Escherichia coli. We recently reported silicatein -cathepsin L chimaeras with the ability to condense silica from solution. These chimaeras are readily obtained by expression in Pichia pastoris, with yields around 40 mg/L of culture. The 1.5 A ° crystal structure of one of these chimaeras allows us to rationalize the catalytic mechanism of silicic acid condensation (Fairhead et al 2008). This is the first report of an enzyme able to precipitate silica by condensation of the putative natural substrate, silicic acid. Characterization of the active site indicates a more likely mechanism than previously proposed by modelling of silicatein for the condensation of alkoxysilanes. Using these chimaeras, it will now be possible to synthesize silica materials from aqueous solution at neutral pH, enabling the co-encapsulation of sensitive biological molecules. The work is immediately relevant to groups studying biomineralization processes and groups synthesizing novel silica structures for application as functional materials, such as enzyme immobilization.