Second-generation products: antibiotics.

There has been outstanding progress in gene cloning from microorganisms producing useful antibiotics. Especially noteworthy is the cloning of a gene for cephalosporin biosynthesis that, with increased copy number, helps to overcome a rate-limiting step in biosynthesis. Although this technology is often fraught with unexpected difficulties, not the least of which is gene expression, yield improvement is a practical application with clear financial benefits to the pharmaceutical industry. Although access to cloned genes for antibiotic biosynthesis is becoming common, expression of the cloned genes in a manner such that yield improvement is achieved is a challenge that will be exciting and beneficial in years to come. Heterologous (interspecies) gene expression in antibiotic-producing microorganisms, particularly the actinomycetes, must be successful if hybrid antibiotics are to be produced. Currently, there are no documented examples of heterologous gene cloning to yield a hybrid antibiotic of utility. Even though a hybrid antibiotic structure has been reported as a result of heterologous gene cloning, the antibiotic is not clinically useful, and the two species used in the experiments are closely related. Although technological advances have enabled successful gene cloning, insufficient attention has been given to the issue of gene expression, particularly heterologous gene expression. The need to develop heterologous gene expression systems is urgent. Until this is done, the inability to express cloned antibiotic biosynthesis genes in heterologous hosts could be a barrier to the generation of useful hybrid antibiotics. The potential for a wide array of new antibiotic compounds that could be generated by gene-cloning technology is vast. At least until the limitations of heterologous gene expression are overcome, the best available screening technology (including molecular and immunological screens) and chemistry might best serve as the most prolific means of discovering useful new antibiotics for agriculture and medicine.