Antimicrobial lipopeptides: in vivo and in vitro synthesis

The non-ribosomally assembled lipopeptides display a number of biological activities, including antibiotic, antitumor, immune-modulating and immune-suppressive activities. This review starts with general comments on antimicrobial peptides (AMPs), a large family of compounds that includes non-ribosomally assembled lipopeptides. Then, it brings together information on in vivo synthesis (biosynthesis) of such hybrid biomolecules using as models the surfactins, potent anionic biosurfactants produced by Bacillus subtilis that have potential environmental and medical applications, but limited productivity due to low yields and the high costs associated with microbial growth and surfactant recovery. It follows a brief statement on how important is to overcome those limitations as well as a discussion about in vitro synthesis (chemical synthesis) of this type of compounds. Hence, the methods currently used for making peptides are outlined and given examples of lipopeptides and analogues that have been chemically synthesized by the solid-phase method using the Fmoc-based chemistry. It becomes clear that most of these compounds have only been successfully produced in small scale and that a challenge is set up to upscale productivity of non-ribosomally assembled lipopeptides with low costs, high yields and, hopefully, using environmental friendly methods, techniques and conditions. In this context, modifications of the protocols used for non-ribosomal synthesis and microwave-assisted chemical synthesis seem to be promising alternatives.