Bioproduction of Depsidones for Pharmaceutical Purposes

Abstract

Lichens are intimate and long-term specific symbioses of photosynthetic algae or cyanobacteria and heterotrophic fungi joined to form a new biological entity different from its individual components (Galun & Kardish, 1995). Mainly chlorolichens produce unique phenolic substances, depside, depsidones and some dibenzofurans, such as usnic acids (Huneck & Yoshimura, 1996), that are not produced by other fungi and plants, and that show some biological activities with interesting applications from a pharmacological point of view, mainly as antiviral agents or for dermatological treatments. Although semisynthetic organic processes have been attempted for the production of depsidones (Elix et al., 1987), they results very tedious, expensive and inappropriate for industrial applications. Alternatively, extraction from lichen thalli collected in nature implies a very high rate of biomass destruction which cannot be balanced because of the very slow rate of growth of these organisms. This last condition also invalidates the use of transgenic specimens. Thus, the use of bioreactors using very small amounts of lichen biomass seems to be as yet the most viable alternative to rapid and efficient production of depsidones. Depsidones are organic compounds consisting of two phenolic acids linked together by both ester and ether bonds. So far, type I polyketide synthases (PKSs) are the suggested catalysts for the biosynthesis of these lichen compounds (Muggia & Grube, 2010). It is generally accepted that depsidones come from depsides, formed by two molecules of orsellinic acid derivatives linked by an ester bond, which means that the formation of ether was carried out on previously formed depsides. Thus, despide and depsidones are closely related and biogenetically they all seem to belong to only one group of chemical structures. It seems to be therefore definite that they are evolved from the same primary compound, the variations being brought about by processes of oxidation and reduction, and other simple reactions (Seshadri, 1944). Polyketide synthases, also known as PKSs, are a family of enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites in bacteria, fungi, plants, and a few animals lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis (Khosla et al., 1999; Jenke-Kodama et al., 2005). The pathway is