1. A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea
- Author
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Chng, Chinping, Lum, Amy M., Vroom, Jonathan A., and Kao, Camilla M.
- Subjects
Erythromycin -- Production processes ,Industrial microorganisms -- Physiological aspects ,Industrial microorganisms -- Genetic aspects ,Genetic regulation -- Evaluation ,Biosynthesis -- Genetic aspects ,Cell differentiation -- Evaluation ,Science and technology - Abstract
Saccharopolyspora erythraea makes erythromycin, an antibiotic commonly used in human medicine. Unusually, the erythromycin biosynthetic (ery) cluster lacks a pathway-specific regulatory gene. We isolated a transcriptional regulator of the ery biosynthetic genes from S. erythraea and found that this protein appears to directly link morphological changes caused by impending starvation to the synthesis of a molecule that kills other bacteria, i.e., erythromycin. DNA binding assays, liquid and affinity chromatography, MALDI-MS analysis, and de novo sequencing identified this protein (Mr = 18 kDa) as the S. erythraea ortholog of BIdD, a key regulator of development in Streptomyces coelicolor. Recombinant S. erythraea BIdD bound to all five regions containing promoters in the ery cluster as well as to its own promoter, the latter with an order-of-magnitude stronger than to the ery promoters. Deletion of bldD in S. erythraea decreased the erythromycin titer in a liquid culture 7-fold and blocked differentiation on a solid medium. Moreover, an industrial strain of S. erythraea with a higher titer of erythromycin expressed more BIdD than a wild-type strain during erythromycin synthesis. Together, these results suggest that BIdD concurrently regulates the synthesis of erythromycin and morphological differentiation. The ery genes are the first direct targets of a BIdD ortholog to be identified that are positively regulated. cell differentiation | secondary metabolites | BIdD
- Published
- 2008