Combinatorial biochemistry in plants: the case of O-methyltransferases

Combinatorial chemistry is common place today in chemical synthesis. Virtua lly thousands of derivatives of a molecule can be achieved by automated sys tems. The use of biological systems to exploit combinatorial chemistry (com binatorial biochemistry) now has multiple examples in the polyketide field. The modular functional domain structure of polyketide synthases have been recombined through genetic engineering into unnatural constellations in het erologous hosts in order to produce polyketide structures not yet discovere d in nature. We present herein an example for a potential type of combinato rial biochemistry in alkaloidal systems using various combinations of Thali ctrum tuberosum (meadow rue) O-methyltransferase subunits that result in he terodimeric enzymes with substrate specificities that differ from those of the homodimeric native enzymes. (C) 2001 Elsevier Science Ltd. All rights r eserved.