Type III Polyketide Synthase Involved in Tropane and Granatane Alkaloid Biosynthesis

Abstract

The lack of data concerning the enzymes and genes responsible for the production of tropane and granatane alkaloids has hindered endeavors to metabolically engineer important pharmacologically active specialized metabolites. It is important to understand how biochemical pathways perform when they originate from evolutionarily diverse families. It is hypothesized that a type III polyketide synthase enzyme is involved in the extension and subsequent cyclization of the second ring in the bicyclic tropane and grantane core structure. This represents a new class of type III polyketide synthases in which the heterocyclic starter molecule is charged and also lacks a Coenzyme A thioester. Putative polyketide synthase enzymes were identified in the Erythroxylum coca and Punica granatum cDNA transcriptome database and heterologously expressed in Pichia pastoris. LC‐MS/MS analysis has revealed the formation of a 4‐(1‐methyl‐2‐pyrrolidinyl)‐3‐oxobutanoate intermediate that is hypothesized to lead to the second ring formation. Understanding how evolutionary changes have occurred in type III polyketide synthases from different metabolic pathways that determine the development and expansion of chemical diversity to produce high valued compounds will be a powerful tool for bioengineering pharmaceuticals.Support or Funding InformationNational Science FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.