Achievements in Combinatorial Biosynthesis

As described above genetic methods to alter the structure of natural products have been developed in the last 10 years. Many new compounds have been generated, some of them with improved characteristics. The genetic approaches to generate novel molecules can be divided into the following categories. 

Targeted gene disruption, involving the inactivation of selected genes, thus generating mutants that accumulate new compounds (50, 70) (Fig. lA). 

Over-expression of a specific gene, followed from unbalancing pathways in order to generate new metabolites (757) (Fig. IB). 

Heterologous co-expression, which involves the expression of two or several 

Tailoring modification, known as metabolic engineering, biotransformation or precursor-directed biosynthesis, involving the feeding of building blocks which are subsequently modified by a specific enzyme involved in the biosynthesis of a structurally related drug (752) (Fig. IF). 

---