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Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins.

Publication ,  Journal Article
Tang, NC; Chilkoti, A
Published in: Nature materials
April 2016

Most genes are synthesized using seamless assembly methods that rely on the polymerase chain reaction (PCR). However, PCR of genes encoding repetitive proteins either fails or generates nonspecific products. Motivated by the need to efficiently generate new protein polymers through high-throughput gene synthesis, here we report a codon-scrambling algorithm that enables the PCR-based gene synthesis of repetitive proteins by exploiting the codon redundancy of amino acids and finding the least-repetitive synonymous gene sequence. We also show that the codon-scrambling problem is analogous to the well-known travelling salesman problem, and obtain an exact solution to it by using De Bruijn graphs and a modern mixed integer linear programme solver. As experimental proof of the utility of this approach, we use it to optimize the synthetic genes for 19 repetitive proteins, and show that the gene fragments are amenable to PCR-based gene assembly and recombinant expression.

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Published In

Nature materials

DOI

EISSN

1476-4660

ISSN

1476-1122

Publication Date

April 2016

Volume

15

Issue

4

Start / End Page

419 / 424

Related Subject Headings

  • Recombinant Proteins
  • Polymerase Chain Reaction
  • Nanoscience & Nanotechnology
  • Genetic Engineering
  • Genes
  • Codon
  • Algorithms
 

Citation

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Tang, N. C., & Chilkoti, A. (2016). Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins. Nature Materials, 15(4), 419–424. https://doi.org/10.1038/nmat4521
Tang, Nicholas C., and Ashutosh Chilkoti. “Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins.Nature Materials 15, no. 4 (April 2016): 419–24. https://doi.org/10.1038/nmat4521.
Tang, Nicholas C., and Ashutosh Chilkoti. “Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins.Nature Materials, vol. 15, no. 4, Apr. 2016, pp. 419–24. Epmc, doi:10.1038/nmat4521.

Published In

Nature materials

DOI

EISSN

1476-4660

ISSN

1476-1122

Publication Date

April 2016

Volume

15

Issue

4

Start / End Page

419 / 424

Related Subject Headings

  • Recombinant Proteins
  • Polymerase Chain Reaction
  • Nanoscience & Nanotechnology
  • Genetic Engineering
  • Genes
  • Codon
  • Algorithms