Metabolic impact assessment for heterologous protein production in Streptomyces lividans based on genome-scale metabolic network modeling

被引：8

作者：

Lule, Ivan ^{[1
]}

D'Huys, Pieter-Jan ^{[1
]}

Van Mellaert, Lieve ^{[2
]}

Anne, Jozef ^{[2
]}

Bernaerts, Kristel ^{[1
]}

Van Impe, Jan ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Dept Chem Engn, Chem & Biochem Proc Technol & Control Sect BioTeC, B-3001 Louvain, Belgium

[2] Katholieke Univ Leuven, Dept Microbiol & Immunol, Lab Mol Bacteriol, B-3001 Louvain, Belgium

来源：

MATHEMATICAL BIOSCIENCES | 2013年 / 246卷 / 01期

关键词：

Streptomyces lividans; (geometric) Flux balance analysis; Mouse tumor necrosis factor (mTNF-alpha); Heterologous proteins; Genome-scale metabolic network; FLUX BALANCE ANALYSIS; NECROSIS-FACTOR-ALPHA; ESCHERICHIA-COLI; SECRETION; OVEREXPRESSION; COELICOLOR;

D O I：

10.1016/j.mbs.2013.08.006

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The metabolic impact exerted on a microorganism due to heterologous protein production is still poorly understood in Streptomyces lividans. In this present paper, based on exometabolomic data, a proposed genome-scale metabolic network model is used to assess this metabolic impact in S. lividans. Constraint-based modeling results obtained in this work revealed that the metabolic impact due to heterologous protein production is widely distributed in the genome of S. lividans, causing both slow substrate assimilation and a shift in active pathways. Exchange fluxes that are critical for model performance have been identified for metabolites of mouse tumor necrosis factor, histidine, valine and lysine, as well as biomass. Our results unravel the interaction of heterologous protein production with intracellular metabolism of S. lividans, thus, a possible basis for further studies in relieving the metabolic burden via metabolic or bioprocess engineering. (C) 2013 Published by Elsevier Inc.

引用

页码：113 / 121

页数：9

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