The past decades, petrochemical refinery processes using fossil-based resources have been used to make a vast amount of chemicals and materials. Due to our increasing concerns on limited availability of fossil resources and the environmental impacts of using these, sustainable production of green chemicals as building blocks has become a vital research area. The ability of thermophilic bacteria to ferment lignocellulose biomass, make them potential production organisms for industrial applications. This PhD thesis focuses on two non-model thermophilic clostridia, the ethanol-producing Hungateiclostridium thermocellum and the succinate-producing Pseudoclostridium thermosuccinogenes. The limited availability of genetic tools for clostridial engineering poses a major barrier for exploiting them as bacterial cell factories. This thesis describes strategies to improve genetic accessibility, advance genetic engineering with CRISPR interference-mediated silencing and improve use of plant-based sugars to pave the way to enhance industrial fermentations.