Genome-scale metabolic network guided engineering of Streptomyces tsukubaensis for FK506 production improvement.

ABSTRACT:

Background

FK506 is an important immunosuppressant, which can be produced by Streptomyces tsukubaensis. However, the production capacity of the strain is very low. Hereby, a computational guided engineering approach was proposed in order to improve the intracellular precursor and cofactor availability of FK506 in S. tsukubaensis.

Results

First, a genome-scale metabolic model of S. tsukubaensis was constructed based on its annotated genome and biochemical information. Subsequently, several potential genetic targets (knockout or overexpression) that guaranteed an improved yield of FK506 were identified by the recently developed methodology. To validate the model predictions, each target gene was manipulated in the parent strain D852, respectively. All the engineered strains sh

SUBMITTER: Huang D 

PROVIDER: S-EPMC3680238 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature