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2 Publications visible to you, out of a total of 2
Predicting strain engineering strategies using iKS1317: a genome‐scale metabolic model of Streptomyces coelicolor

Abstract

Not specified

Authors: Tjaša Kumelj, Snorre Sulheim, Alexander Wentzel, Eivind Almaas

Date Published: 7th Dec 2018

Publication Type: Not specified

Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters

Abstract (Expand)

We have constructed derivatives of Streptomyces coelicolor M145 as hosts for the heterologous expression of secondary metabolite gene clusters. To remove potentially competitive sinks of carbon and … nitrogen, and to provide a host devoid of antibiotic activity, we deleted four endogenous secondary metabolite gene clusters from S. coelicolor M145--those for actinorhodin, prodiginine, CPK and CDA biosynthesis. We then introduced point mutations into rpoB and rpsL to pleiotropically increase the level of secondary metabolite production. Introduction of the native actinorhodin gene cluster and of gene clusters for the heterologous production of chloramphenicol and congocidine revealed dramatic increases in antibiotic production compared with the parental strain. In addition to lacking antibacterial activity, the engineered strains possess relatively simple extracellular metabolite profiles. When combined with liquid chromatography and mass spectrometry, we believe that these genetically engineered strains will markedly facilitate the discovery of new compounds by heterologous expression of cloned gene clusters, particularly the numerous cryptic secondary metabolic gene clusters that are prevalent within actinomycete genome sequences.

Authors: Juan Pablo Gomez-Escribano, Mervyn J. Bibb

Date Published: 1st Mar 2011

Publication Type: Not specified

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