Antibiotics diversification

In this chapter, we will examine strategies for producing antibiotics. We have had to be selective and have chosen to confine discussion largely to the -lactams, with particular emphasis on the diversification of the primary antibiotics using biotransformation. We have adopted this strategy in order to produce a manageable study, while enabling us to explain the main principles involved. 

The polyketides are a large family of bio synthetically related NPs, some of which have very great pharmaceutical value (polyketide sales total about 10 billion annually, see also Chapter 7). Some antibiotics (erythromycin, monensin, rifamycin), immunosuppressants (rapamycin), antifungal substances (amphotericin), antiparasitic (aver-mectin) and anticancer drugs (doxorubicin) are polyketides. The term polyketide refers to the fact that the basic carbon skeleton is not a simple hydrocarbon chain as in the case of fatty acids but is a series of linked keto groups in sequence (Figure 3.6). The first phase of this pathway, the generation of carbon skeleton diversification. 

We will begin by giving a brief overview of foe strategies that may be employed to produce desirable antibiotics. Then we will give a brief review of the history of the production of penicillin. We will foen examine foe mode of action of P-lactam antibiotics and briefly describe foe biosynthetic pathways of P-lactam antibiotic production. Subsequently we will examine, in greater depth, the biotransformation of penicillins. A consideration of cephalsporin production will follow and will be ccMnpared with foe production and diversification of penicillins. In foe final part of this chapter we will briefly describe foe new P-lactams. 

---