Progress toward a reduced phage genetic code

Anzhi Yao, Sean A. Reed, Minseob Koh, Chenguang Yu, Xiaozhou Luo, Angad P. Mehta, Peter G. Schultz

Research output: Contribution to journalArticlepeer-review


All known living organisms use at least 20 amino acids as the basic building blocks of life. Efforts to reduce the number of building blocks in a replicating system to below the 20 canonical amino acids have not been successful to date. In this work, we use filamentous phage as a model system to investigate the feasibility of removing methionine (Met) from the proteome. We show that all 24 elongation Met sites in the M13 phage genome can be replaced by other canonical amino acids. Most of these changes involve substitution of methionine by leucine (Leu), but in some cases additional compensatory mutations are required. Combining Met substituted sites in the proteome generally led to lower viability/infectivity of the mutant phages, which remains the major challenge in eliminating all methionines from the phage proteome. To date a total of 15 (out of all 24) elongation Mets have been simultaneously deleted from the M13 proteome, providing a useful foundation for future efforts to minimize the genetic code.

Original languageEnglish (US)
Pages (from-to)5247-5252
Number of pages6
JournalBioorganic and Medicinal Chemistry
StatePublished - Oct 15 2018
Externally publishedYes


  • Amino acid alphabet reduction
  • Bacteriophage M13
  • DNA library
  • Methionine substitution

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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