Strategies for manipulation of genes in microbes for production of beta-lactam antibiotics

The deployment of recombinant DNA techniques to beta-lactam antibiotic prod ucing fungi and various Streptomyces spp. have made it possible to understa nd in considerable details, the biosynthetic pathways, the mechanism of syn thesis, and the genes involved in the process, As a result, it is becoming possible to manipulate the individual gene or cluster of genes and thereby the pathways in order to develop microbes which can produce beta-lactams at rates higher than the traditional strains. By the judicious incorporation of genes such as cef E of Streptomyces clavuligerus into Penicillium chryso genum it has been possible to produce the cephalosporin intermediate, 7-ami no-3-deacetoxycephalosporanic acid (7-ADCA) in the fermenters. The incorpor ation of VHb gene in Acremonium chrysogenum increased the productivity of t he strain for cephalosporin C, The understanding of the substrate specifici ty of pcb C genes has enabled the synthesis of complex beta-lactams from a variety of synthetic tripeptides, The future years are expected to witness the mixing, shuttling, and reshuffling of bacterial and fungal genes among themselves and the maximization of expression of the target gene(s) by modi fying the regulatory and the control mechanisms of the biosynthetic pathway s in order to synthesize the target beta-lactam molecules at economic costs by engineered microbes.