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Principal component analysis of proteomics (PCAP) as a tool to direct metabolic engineering.
Alonso-Gutierrez, Jorge; Kim, Eun-Mi; Batth, Tanveer S; Cho, Nathan; Hu, Qijun; Chan, Leanne Jade G; Petzold, Christopher J; Hillson, Nathan J; Adams, Paul D; Keasling, Jay D; Garcia Martin, Hector; Lee, Taek Soon.
Afiliação
  • Alonso-Gutierrez J; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Kim EM; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Batth TS; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Cho N; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
  • Hu Q; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
  • Chan LJG; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Petzold CJ; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Hillson NJ; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Adams PD; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
  • Keasling JD; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineerin
  • Garcia Martin H; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: hgmartin@lbl.gov.
  • Lee TS; Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: tslee@lbl.gov.
Metab Eng ; 28: 123-133, 2015 Mar.
Article em En | MEDLINE | ID: mdl-25554074
ABSTRACT
Targeted proteomics is a convenient method determining enzyme expression levels, but a quantitative analysis of these proteomic data has not been fully explored yet. Here, we present and demonstrate a computational tool (principal component analysis of proteomics, PCAP) that uses quantitative targeted proteomics data to guide metabolic engineering and achieve higher production of target molecules from heterologous pathways. The method is based on the application of principal component analysis to a collection of proteomics and target molecule production data to pinpoint specific enzymes that need to have their expression level adjusted to maximize production. We illustrated the method on the heterologous mevalonate pathway in Escherichia coli that produces a wide range of isoprenoids and requires balanced pathway gene expression for high yields and titers. PCAP-guided engineering resulted in over a 40% improvement in the production of two valuable terpenes. PCAP could potentially be productively applied to other heterologous pathways as well.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Terpenos / Regulação Bacteriana da Expressão Gênica / Proteínas de Escherichia coli / Proteômica / Escherichia coli / Engenharia Metabólica Idioma: En Revista: Metab Eng Assunto da revista: ENGENHARIA BIOMEDICA / METABOLISMO Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Terpenos / Regulação Bacteriana da Expressão Gênica / Proteínas de Escherichia coli / Proteômica / Escherichia coli / Engenharia Metabólica Idioma: En Revista: Metab Eng Assunto da revista: ENGENHARIA BIOMEDICA / METABOLISMO Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos