Artificial multi-enzyme cascades bear great potential for offering sustainable synthesis of useful and valuable natural molecules. In the past two years, many new cascades were developed to produce natural alcohols, acids, esters, amino compounds, fatty acid derivatives, alkaloids, terpenoids, terpenes and monosaccharides from natural substrates and simple chemicals, respectively. These artificial cascades were constructed by combining individual enzymes designed using the retro-synthesis strategy and based on the available natural substrates and simple chemicals. While performing the cascades in vivo is often simple and straightforward, in vitro cascades usually require cofactor regeneration that was achieved by introducing one or more cofactor-regeneration modules in one pot. Protein engineering is frequently used to improve the performances of some enzymes in the cascades. © 2022 Elsevier Ltd