Biosynthetic engineering for the assembly of better drugs

The declining prospects of innovator pharmaceutical companies have been attributed to their inability to discover leads that bind to novel protein domains. All of the 21,000-odd drug products that have ever been approved by the US FDA bind to just 130 of the over 10,000 functional protein domains that exist in the human body. The high degree of drug redundancy, in turn, stems from the industry’s persistence with combinatorial chemistry to synthesize drug candidates. Not only is the chemical space being screened for biological activity usually one that has been previously interrogated, but the products of combinatorial chemistry too are simply not drug-like. So dire are the odds that launching a single synthetic compound necessitates screening as many as 100,000 molecules from a combinatorial library.