A supplement providing a snapshot of the latest developments in chemical biology
Understanding lignan synthesis
14 February 2006
Researchers in the US are closer to understanding the synthesis of plant-derived compounds with antiviral and anticancer properties.
The key enzyme involved in the synthesis of (-)-matairesinol is secoisolariciresinol dehydrogenase (SDH), which converts (-)-secoisolariciresinol into (-)-matairesinol by means of the coenzyme nicotinamide adenine dinucleotide (NAD+) in a hydride transfer process.
Lewis and his team introduced specific mutations into the SDH gene to examine the effects of changing certain amino acids on the SDH enzyme activity. Substituting either the tyrosine in position 167 or the lysine in position 171 with alanine resulted in total loss of enzyme activity. Substituting the serine in position 153 with alanine stopped the reaction half-way through, forming small amounts of an intermediate lactol compound. These amino acids must therefore be involved in the active site of the enzyme, said Lewis.
The work could make it easier to metabolically engineer useful 'lignans in foodstuffs or of antiviral/anticancer lignans, such as podophyllotoxin' said Lewis.