Lignocellulose is the most abundant renewable natural resource on earth and
has been successfully used for the production of biofuels. A significant challenge is to develop
cost-effective, environmentally friendly and efficient processes for the conversion
of lignocellulose materials into suitable substrates for biotransformation. A number of approaches
have been explored to convert lignocellulose into sugars, e.g. combining chemical
pretreatment and enzymatic hydrolysis. In nature, there are organisms that can transform
the complex lignocellulose efficiently, such as wood-degrading fungi (brown rot and
white rot fungi), bacteria (e.g. Clostridium thermocellum), arthropods (e.g. termite) and
certain animals (e.g. ruminant). Here, we highlight recent case studies of the natural degraders
and the mechanisms involved, providing new utilities in biotechnology. The sugars
produced from such biotransformations can be used in metabolic engineering and synthetic
biology for the complete biosynthesis of natural medicine. The unique opportunities
in using lignocellulose directly to produce natural drug molecules with either using mushroom
and/or ‘industrial workhorse’ organisms (Escherichia coli and Saccharomyces cerevisiae)
will be discussed.