MOSAIC Synthesizes 1,000-Plus DNA Fragments in One Pot, Enabling Higher-Potency PETase Variants
Updated
Updated · Nature.com · Aug 19
MOSAIC Synthesizes 1,000-Plus DNA Fragments in One Pot, Enabling Higher-Potency PETase Variants
1 articles · Updated · Nature.com · Aug 19
Summary
Researchers report MOSAIC, a hybridization-driven DNA synthesis method that generated more than 1,000 distinct gene fragments in a single one-pot reaction.
The approach pairs orthogonal self-assembly of overlapping oligonucleotides in vitro with host-cell DNA repair in vivo, reducing crosstalk and delivering near-zero fragment misalignment while keeping synthesis errors controllable.
Microchip-based oligonucleotide production underpins the scale-up, and the paper says the method can assemble fragments from 300 base pairs to 3,000 base pairs, with a maximum demonstrated assembly of 9.9 kb.
Using those large variant libraries, the team engineered PETase enzymes and identified variants with higher activity than the current gold-standard enzyme.
The advance targets a core synthetic-biology bottleneck by making parallel gene writing and protein engineering faster and more scalable.
Could Tsinghua's new MOSAIC technology disrupt a multibillion-dollar DNA synthesis market and dethrone current biotech giants?
Will the open-source release of MOSAIC's code accelerate a new era of custom-built enzymes capable of erasing global plastic waste?
What hidden biological biases might emerge when scientists rely on living cells to repair massive synthetic DNA libraries?
Breaking the Plastic Bottleneck: How MOSAIC DNA Synthesis and AI-Driven Biofoundries Are Transforming Enzyme Engineering and Recycling
Overview
This report highlights the revolutionary MOSAIC technology, which enables fast, low-cost, and highly accurate DNA synthesis by using reversible hybridization instead of traditional error-prone enzymatic reactions. By allowing thousands of gene fragments to be assembled in a single step, MOSAIC overcomes the limitations of older chemical methods that require stitching short DNA pieces together and often introduce errors. This breakthrough not only democratizes synthetic biology but also accelerates the discovery of powerful enzymes, such as those that can degrade plastics, paving the way for innovative solutions to global environmental challenges.