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Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus

Paper ID Volume ID Publish Year Pages File Format Full-Text
31502 44803 2016 9 PDF Available
Title
Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus
Abstract

•Streptomyces albus genome explained high salinomycin yield in oil-rich medium.•Quantitation of acyl-CoA esters identified limiting factors and engineered targets.•Cluster deletions and ethylmalonyl-CoA over-expression improved salinomycin titer.

The anticoccidial salinomycin is a polyketide produced by Streptomyces albus and requires malonyl-CoAs, methylmalonyl-CoAs, and ethylmalonyl-CoAs for the backbone assembly. Genome sequencing of S. albus DSM 41398 revealed a high percentage of genes involved in lipid metabolism, supporting the high salinomycin yield in oil-rich media. Seven PKS/PKS-NRPS gene clusters in the genome were found to be actively transcribed and had been individually deleted, which resulted in significantly improved salinomycin production. However, a combined deletion of PKS-NRPS-2 and PKS-6 showed no further improvement. Whereas the concentrations of malonyl-CoA and methylmalonyl-CoA were increased, the concentration of ethylmalonyl-CoA remained low in the mutants. An endogenous crotonyl-CoA reductase gene (ccr) was overexpressed in the ΔPKS-NRPS-2/ΔPKS-6 mutant, resulting in improved production. Combination of cluster deletions and over-expression of ccr gene led to an overall titer improvement of salinomycin from 0.60 to 6.60 g/L. This engineering strategy can be implemented for various natural polyketides production.

Keywords
Salinomycin; Genome; Extender unit; Crotonyl-CoA reductase; Polyketide
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Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 35, May 2016, Pages 129–137
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
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Price after discount Only $4.95
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