A method for producing buta‐1,3‐diene (1,3‐BD) by an amalgamation of chemical and biological approaches with syngas as the carbon source is proposed. Syngas is converted to the central intermediate, acetyl‐CoA, by microorganisms through a tetrahydrofolate metabolism pathway. Acetyl‐CoA is subsequently converted to malonyl‐CoA using a carbonyl donor in the presence of a carboxylase enzyme. A decarboxylative Claisen condensation of malonyl‐CoA and acetaldehyde ensues in the presence of acyltransferases to form 3‐hydroxybutyryl‐CoA, which is subsequently reduced by aldehyde reductase to give butane‐1,3‐diol (1,3‐BDO). An ensuing dehydration step converts 1,3‐BDO to 1,3‐BD in the presence of a chemical dehydrating reagent.