Genetically engineered Streptomyces clavuligerus strains with improved
capabilities to produce clavulanic acid are provided. The strains are
genetically engineered by disrupting newly identified
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes. This results in
an increased intracelluar pool of the clavulanic acid precursor
D-glyceraldehyde-3-phosphate (D-G3P), and increased clavulanic acid
production. Clavulanic acid production may be further increased by
supplying arginine to the medium in which the S. clavuligerus is grown.