title: Coordination of glycerol utilization and clavulanic acid biosynthesis to improve clavulanic acid production in Streptomyces clavuligerus.
abstract: The glycerol utilization (gyl) operon is involved in clavulanic acid (CA) production by Streptomyces clavuligerus, and possibly supplies the glyceraldehyde-3-phosphate (G3P) precursor for CA biosynthesis. The gyl operon is regulated by GylR and is induced by glycerol. To enhance CA production in S. clavuligerus, an extra copy of ccaR expressed from Pgyl (the gyl promoter) was integrated into the chromosome of S. clavuligerus NRRL 3585. This construct coordinated the transcription of CA biosynthetic pathway genes with expression of the gyl operon. In the transformants carrying the Pgyl-controlled regulatory gene ccaR, CA production was enhanced 3.19-fold in glycerol-enriched batch cultures, relative to the control strain carrying an extra copy of ccaR controlled by its own promoter (PccaR). Consistent with enhanced CA production, the transcription levels of ccaR, ceas2 and claR were significantly up-regulated in the transformants containing Pgyl-controlled ccaR.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Dekun
authors.initials: D
authors.lastname: Guo
authors.forename: Youbao
authors.initials: Y
authors.lastname: Zhao
authors.forename: Keqian
authors.initials: K
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019818:Clavulanic Acid / Q000096:biosynthesis*; D004926:Escherichia coli / Q000378:metabolism; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005986:Glyceraldehyde 3-Phosphate / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism*; D005810:Multigene Family; D009841:Oligonucleotides / Q000235:genetics; D009876:Operon; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013302:Streptomyces / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009841:Oligonucleotides; D005986:Glyceraldehyde 3-Phosphate; D019818:Clavulanic Acid; D005990:Glycerol