Natural product chemistry meets genetics: when is a genotype a chemotype?

The chemotype of a microbial or plant species has traditionally been defined as its profile of natural products, and the genotype has been defined as its genetic constitution or DNA sequence. The purpose of this perspective is to discuss applications of DNA genotyping, particularly by polymerase chain reaction (PCR)-amplification methods, to predicting natural product chemotypes of fungi and plants of importance in food and agriculture. Development of PCR genotyping for predicting chemotypes will require collaboration between molecular biologists and natural product chemists, as well as community standards for reporting data. PCR genotyping should be validated by chemical analysis of individuals that represent the allelic diversity of the target gene in the population. To avoid misinterpretation, it is critical to differentiate data obtained by genotyping from data obtained by chemical analysis. The obvious and appropriate solution is to retain the established meanings of genotype and chemotype, both of which have been in use for half a century in the fields of genetics and natural product chemistry.