Recent trends in the biochemistry of surfactin

The name surfactin refers to a bacterial cyclic lipopeptide, primarily reno wned for its exceptional surfactant power since it lowers the surface tensi on of water from 72 mN m(-1) to 27 mN m(-1) at a concentration as low as 20 mu M. Although surfactin was discovered about 30 years ago, there has been a revival of interest in this compound over the past decade, triggered by an increasing demand for effective biosurfactants for difficult contemporar y ecological problems. This simple molecule also looks very promising as an antitumoral, antiviral and anti-Mycoplasma agent. Structural characteristi cs show the presence of a heptapeptide with an LLDLLDL chiral sequence link ed, via a lactone bond, to a beta-hydroxy fatty acid with 13-15 C atoms. In solution, the molecule exhibits a characteristic "horse saddle" conformati on that accounts for its large spectrum of biological activity, making it v ery attractive for both industrial applications and academic studies. Surfa ctin biosynthesis is catalysed non-ribosomally by the action of a large mul tienzyme complex consisting of four modular building blocks, called the sur factin synthetase. The biosynthetic activity involves the multicarrier thio -template mechanism and the enzyme is organized in structural domains that place it in the family of peptide synthetases, a class of enzymes involved in peptidic secondary-metabolite synthesis. The srfA operon, the sfp gene e ncoding a 4'-phosphopantetheinyltransferase and the comA regulatory gene wo rk together for surfactin biosynthesis, while the gene encoding the acyltra nsferase remains to be isolated. Concerning surfactin production, there is no indication whether the genetic regulation, involving a quorum-sensing me chanism, overrides other regulation factors promoted by the fermentation co nditions. Knowledge of the modular arrangement of the peptide synthetases i s of the utmost relevance to combinatorial biosynthetic approaches and has been successfully used at the gene level to modify the surfactin template. Biosynthetic and genetic rationales have been described for building varian ts. A fine study of the structure/function relationships associated with th e three-dimensional structure has led to the recognition of the specific re sidues required for activity. These studies will assist researchers in the selection of molecules with improved and/or refined properties useful in oi l and biomedical industries.