While our results show the feasibility of the enzyme cascade, the supply of the co-substrate SAM is a limitation. Stoichiometric addition is not economically feasible for the synthesis of monomers. In the last years, different multi-enzyme cascade reactions have been developed for the regeneration of SAM or its in situ formation from inexpensive precursors. Halide methyltransferases transfer methyl groups from methyl iodide to SAH and their activity could be improved by directed enzyme evolution. The enzymatic approach has the advantage that the problematic methyl iodide can be applied in small concentrations. SAM is produced from L-methionine and ATP. This was exploited in a multi-enzyme cascade of six enzymatic steps that couples regeneration of SAM to enzymatic polyphosphate degradation. Similarly, the bacterial metabolism can be used to supply SAM in whole-cell biocatalysts. Recently, the intracellular supply of SAM was improved by betaine as the methyl source by introducing a betaine-homocysteine methyltransferase and coupling it to S-adenosyl-L-homocysteine (SAH) hydrolysis pathways, underlining the feasibility to supply SAM in whole-cell biocatalysts. The rapid progress in the regeneration of SAM raises the expectation that the improvements needed for the synthesis of biobased chemicals can be achieved in the near future.