Biosynthesis of Medium-Sized Molecules

BIOSYNTHESIS OF MEDIUM-SIZED MOLECULES

Although we have covered the production of alcohol and of indigo, so far we have really been considering degradative pathways. The fermentation schemes that produce alcohol are designed to release energy from sugars, and indigo is an incidental by-product of the naphthalene degradation system. However, a variety of natural products are made industrially that rely on genuine biosynthetic pathways. For example, many amino acids are manufactured by microorganisms and used for a variety of purposes. Here we will discuss the synthesis of somewhat more sophisticated molecules. We will first look at selected sterols and antibiotics and then consider some examples of biopolymers. The objective is not to cover these pathways in detail but to provide examples of how genetic engineering can be used to improve these processes.

Although antibiotics and sterols are molecules of only intermediate complexity, they are the most difficult to tackle by genetic engineering. The reason is that their synthetic pathways may have 20 or more steps. Each step requires a separate enzyme, encoded by its own gene. In addition, many of these pathways are branched and/or interact with other metabolic pathways. Consequently, their regulation is often complex. Analyzing, cloning, and expressing all the genes that encode the enzymes and regulatory proteins for long and complex pathways requires a great deal of effort.