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Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process
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Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process
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Journal Article
Heterologous expression of oxytetracycline biosynthetic gene cluster in Streptomyces venezuelae WVR2006 to improve production level and to alter fermentation process
2016
Overview
Heterologous expression is an important strategy to activate biosynthetic gene clusters of secondary metabolites. Here, it is employed to activate and manipulate the oxytetracycline (OTC) gene cluster and to alter OTC fermentation process. To achieve these goals, a fast-growing heterologous host
Streptomyces venezuelae
WVR2006 was rationally selected among several potential hosts. It shows rapid and dispersed growth and intrinsic high resistance to OTC. By manipulating the expression of two cluster-situated regulators (CSR) OtcR and OtrR and precursor supply, the OTC production level was significantly increased in this heterologous host from 75 to 431 mg/l only in 48 h, a level comparable to the native producer
Streptomyces rimosus
M4018 in 8 days. This work shows that
S. venezuelae
WVR2006 is a promising chassis for the production of secondary metabolites, and the engineered heterologous OTC producer has the potential to completely alter the fermentation process of OTC production.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
Anti-Bacterial Agents - biosynthesis
/ Applied Genetics and Molecular Biotechnology
/ Bacteria
/ Biomedical and Life Sciences
/ Biosynthetic Pathways - genetics
/ E coli
/ Genes
/ genetically modified organisms
/ heterologous gene expression
/ hosts
/ Microbial Genetics and Genomics
/ Oxytetracycline - biosynthesis
/ Plasmids
/ Streptomyces - growth & development
/ Studies
