High solubility of random-sequence proteins consisting of five kinds of primitive amino acids

Nobuhide Doi, Koichi Kakukawa, Yuko Oishi, Hiroshi Yanagawa

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Searching for functional proteins among random-sequence libraries is a major challenge of protein engineering; the difficulties include the poor solubility of many random-sequence proteins. A library in which most of the polypeptides are soluble and stable would therefore be of great benefit. Although modern proteins consist of 20 amino acids, it has been suggested that early proteins evolved from a reduced alphabet. Here, we have constructed a library of random-sequence proteins consisting of only five amino acids, Ala, Gly, Val, Asp and Glu, which are believed to have been the most abundant in the prebiotic environment. Expression and characterization of arbitrarily chosen proteins in the library indicated that five-alphabet random-sequence proteins have higher solubility than do 20-alphabet random-sequence proteins with a similar level of hydrophobicity. The results support the reduced-alphabet hypothesis of the primordial genetic code and should also be helpful in constructing optimized protein libraries for evolutionary protein engineering.

Original languageEnglish
Pages (from-to)279-284
Number of pages6
JournalProtein Engineering, Design and Selection
Volume18
Issue number6
DOIs
Publication statusPublished - 2005 Jun

Fingerprint

Solubility
Amino acids
Proteins
Amino Acids
Libraries
Protein Engineering
Genetic Code
Prebiotics
Hydrophobic and Hydrophilic Interactions
Polypeptides
Hydrophobicity
Peptides

Keywords

  • Genetic code
  • Protein design
  • Protein evolution
  • Reduced amino acid alphabet
  • Synthetic library

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology

Cite this

High solubility of random-sequence proteins consisting of five kinds of primitive amino acids. / Doi, Nobuhide; Kakukawa, Koichi; Oishi, Yuko; Yanagawa, Hiroshi.

In: Protein Engineering, Design and Selection, Vol. 18, No. 6, 06.2005, p. 279-284.

Research output: Contribution to journalArticle

Doi, Nobuhide ; Kakukawa, Koichi ; Oishi, Yuko ; Yanagawa, Hiroshi. / High solubility of random-sequence proteins consisting of five kinds of primitive amino acids. In: Protein Engineering, Design and Selection. 2005 ; Vol. 18, No. 6. pp. 279-284.
@article{09f4e95ef0c142ec8d32a32b11532e0a,
title = "High solubility of random-sequence proteins consisting of five kinds of primitive amino acids",
abstract = "Searching for functional proteins among random-sequence libraries is a major challenge of protein engineering; the difficulties include the poor solubility of many random-sequence proteins. A library in which most of the polypeptides are soluble and stable would therefore be of great benefit. Although modern proteins consist of 20 amino acids, it has been suggested that early proteins evolved from a reduced alphabet. Here, we have constructed a library of random-sequence proteins consisting of only five amino acids, Ala, Gly, Val, Asp and Glu, which are believed to have been the most abundant in the prebiotic environment. Expression and characterization of arbitrarily chosen proteins in the library indicated that five-alphabet random-sequence proteins have higher solubility than do 20-alphabet random-sequence proteins with a similar level of hydrophobicity. The results support the reduced-alphabet hypothesis of the primordial genetic code and should also be helpful in constructing optimized protein libraries for evolutionary protein engineering.",
keywords = "Genetic code, Protein design, Protein evolution, Reduced amino acid alphabet, Synthetic library",
author = "Nobuhide Doi and Koichi Kakukawa and Yuko Oishi and Hiroshi Yanagawa",
year = "2005",
month = "6",
doi = "10.1093/protein/gzi034",
language = "English",
volume = "18",
pages = "279--284",
journal = "Protein Engineering, Design and Selection",
issn = "1741-0126",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - High solubility of random-sequence proteins consisting of five kinds of primitive amino acids

AU - Doi, Nobuhide

AU - Kakukawa, Koichi

AU - Oishi, Yuko

AU - Yanagawa, Hiroshi

PY - 2005/6

Y1 - 2005/6

N2 - Searching for functional proteins among random-sequence libraries is a major challenge of protein engineering; the difficulties include the poor solubility of many random-sequence proteins. A library in which most of the polypeptides are soluble and stable would therefore be of great benefit. Although modern proteins consist of 20 amino acids, it has been suggested that early proteins evolved from a reduced alphabet. Here, we have constructed a library of random-sequence proteins consisting of only five amino acids, Ala, Gly, Val, Asp and Glu, which are believed to have been the most abundant in the prebiotic environment. Expression and characterization of arbitrarily chosen proteins in the library indicated that five-alphabet random-sequence proteins have higher solubility than do 20-alphabet random-sequence proteins with a similar level of hydrophobicity. The results support the reduced-alphabet hypothesis of the primordial genetic code and should also be helpful in constructing optimized protein libraries for evolutionary protein engineering.

AB - Searching for functional proteins among random-sequence libraries is a major challenge of protein engineering; the difficulties include the poor solubility of many random-sequence proteins. A library in which most of the polypeptides are soluble and stable would therefore be of great benefit. Although modern proteins consist of 20 amino acids, it has been suggested that early proteins evolved from a reduced alphabet. Here, we have constructed a library of random-sequence proteins consisting of only five amino acids, Ala, Gly, Val, Asp and Glu, which are believed to have been the most abundant in the prebiotic environment. Expression and characterization of arbitrarily chosen proteins in the library indicated that five-alphabet random-sequence proteins have higher solubility than do 20-alphabet random-sequence proteins with a similar level of hydrophobicity. The results support the reduced-alphabet hypothesis of the primordial genetic code and should also be helpful in constructing optimized protein libraries for evolutionary protein engineering.

KW - Genetic code

KW - Protein design

KW - Protein evolution

KW - Reduced amino acid alphabet

KW - Synthetic library

UR - http://www.scopus.com/inward/record.url?scp=21744445913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21744445913&partnerID=8YFLogxK

U2 - 10.1093/protein/gzi034

DO - 10.1093/protein/gzi034

M3 - Article

C2 - 15928003

AN - SCOPUS:21744445913

VL - 18

SP - 279

EP - 284

JO - Protein Engineering, Design and Selection

JF - Protein Engineering, Design and Selection

SN - 1741-0126

IS - 6

ER -