THE ARGG GENE OF STREPTOMYCES-CLAVULIGERUS HAS LOW HOMOLOGY TO UNSTABLE ARGG FROM OTHER ACTINOMYCETES - EFFECT OF AMPLIFICATION ON CLAVULANIC ACID BIOSYNTHESIS

The argG gene of Streptomyces clavuligenus (Scl) has been cloned by co mplementation of argG mutants of Escherichia coli and S. lividans (Sl) . The argG nucleotide (nt) sequence showed that it corresponds to a ne w type of argG different from the corresponding genes of S. coelicolor (Sco) and Sl. It encodes a 43 250-Da protein that showed higher simil arity to argininosuccinate synthetases (ASS) from Methanococcus vannie lii and Methanosarcina barkeri than to ASS deduced from other Streptom yces argG. No hybridization of the Sd argG was found with the homologo us genes of Sl or Sco. The argH gene was located downstream from argG in Scl. The genomic region around argG and argH in Sd was different fr om the homologous regions in other Streptomyces and is not genetically unstable, unlike in Sco and Sl. Amplification of argG in transformant Scl[pULAR113] results in a 2.3-fold increase in the production of cla vulanic acid (CA) in relation to the control strain Scl[pIJ699].