Science 359, 343–347 (2018)

Gene synthesis is essential for protein designs and many other applications of genes. However, gene synthesis is much less developed compared to gene sequencing and the current step-by-step sewing synthesis approach is quite expensive. Now, Plesa et al. report a much cheaper one-pot method called DropSynth by which they can synthesize multiple genes in parallel from an oligonucleotide microarray.

The DropSynth approach uses barcoded microbeads to pull down the desired oligonucleotides with complementary barcodes from the oligo microarray. The microbeads with captured oligonucleotides are subsequently emulsified into picolitre droplets, where full-length genes with the desired sequences are assembled via polymerase cycling assembly. The resulting sequences are then released from the emulsion droplets by type-IIS restriction enzyme sites. Thousands of synthetic genes that encode homologs of two E. coli proteins have been successfully synthesized. The capability of the protein homologs to complement certain functions has been tested using multiplexed functional assays. These results can help improve the understanding of the sequence–function relationship. The DropSynth method requires no specialized equipment, enabling access to a gene pool at a price similar to an oligonucleotide pool. However, one should note that although it is advantageous to obtain large libraries of genes, the method’s efficiency to produce a particular gene is too low, which should be improved to meet manufacturing needs.