There is a high societal need for a sustainable production of key chemistry, food and health care compounds. Microbial cell factories are logical production systems, but up to now they use sugars and other food derived raw materials as substrates. Sugars originating from plants demand cultivable land which is more and more needed for human nutrition. Methanol - with a worldwide production capacity of more than 46 million tons per year - is regarded as an alternative highly attractive raw material in microbial fermentation for the manufacturing of special, fine, bulk, and fuel chemicals. This is especially true for the EU market, where industrial biotechnology still is hampered by strict use and price regulations as well as import limitations for agricultural commodities, such as corn or sugar. The supply of methanol can base upon both fossil and renewable resources, rendering it a highly flexible and sustainable raw material. Our vision is a viable methanol-based European bio-economy, which we will promote by for the first time applying synthetic biology principles for cell factory development in order to harness methanol as a general feedstock for the manufacturing of special and fine chemicals. In nature, methylotrophic microorganisms can utilize methanol as their sole source of carbon and energy. The project PROMYSE will deliver an alternative route to sought-after chemicals, with a major focus on terpenoids. PROMYSE combines two frontline research topics: orthogonal modularization of methylotrophy within a Synthetic Biology concept and employing methanol as a feedstock for biotechnological production. Through the transfer of methylotrophy modules, Synthetic Biology will pave the way to capitalize on the metabolic versatility and engineered production pathways of genetically well tractable microorganisms, such as E. coli, B. subtilis and C. glutamicum for biotransformation from methanol.