Evidence map›Paper›PMID 26726995›Full record

ArticleNature materials2016

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

Nicholas C Tang, Ashutosh Chilkoti

Abstract read
In one paragraph

Article in Nature materials, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
  2. Technologies for engineering repetitive DNA.Quantitative biology (Beijing, China) · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Synthetic Biomolecular Condensates: Design Principles and Applications.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  8. Article
  9. Nonfouling Coatings from Synthetic Intrinsically Disordered Proteins.Small (Weinheim an der Bergstrasse, Germany) · 2025
    Article
  10. A Novel Gene Synthesis Platform for Designing Functional Protein Polymers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  11. Microbial Production of High-Performance Fibers from Muscle Protein Titin.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Contribution of the ELRs to the development of advancedFrontiers in bioengineering and biotechnology · 2024
    Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Nicholas C TangDepartment of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.ORCID http://orcid.org/0000-0003-0162-9743
Ashutosh ChilkotiDepartment of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
Duke University · US

Funding

University Training Program in Biomolecular & Tissue EngineeringT32GM008555 · NIGMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 1994 to 2021
$8.1M
ELASTIN FUSION PROTEINSR01GM061232 · NIGMS · DUKE UNIVERSITY · PI CHILKOTI, ASHUTOSH · 2000 to 2017
$4.6M
NIGMS NIH HHS GM061232NIGMS NIH HHS R01 GM061232NIGMS NIH HHS T32 GM008555
6 · The paper itself

Abstract

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.

Indexed as

AlgorithmsGenesCodonGenetic EngineeringPolymerase Chain ReactionRecombinant ProteinsCodonRecombinant Proteins

Identifiers

PMID26726995
PMCPMC4809025
OpenAlexW2258324010

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.