A consortium of cross-disciplinary research groups have come together at Los Alamos with the aim of combining unique experimental and theoretical capabilities and expertise to find innovative and new solutions to improve the cost and efficiency of producing biofuels. A primary focus has been the investigation of different approaches to ‘pre-treatments’ such as using ammines, ionic liquids, and other approaches based on enzymes and small biological molecules derived from fungi. For example, the white rot fungus Phanerochaete chrysosporium utilizes a number of secreted peroxidases, in combination with small molecule cofactors and mediators, to catalyze the degradation reaction.  We will present our results from various microscopy imaging, neutron and X-ray diffraction, synthetic chemistry, enzymology, mass spectrometry and theoretical modeling approaches to understanding and optimizing biomass pre-treatment processes.