Texas Tech University
TTU HomeDepartment of Chemistry and Biochemistry Faculty Dr. John D'Auria

Dr. John D'Auria

Title:

Assistant Professor

Education:

Ph.D. University of Michigan, 2002; Alexander von Humboldt Postdoctoral Fellow 2003-2005, Project Leader; Max Planck Institute for Chemical Ecology, 2005-2013

Research Area:

Biochemistry

Office:

Phone:

Email:

More Info:

Chemistry-CHEM 413-D

806-834-7348

john.c.dauria@ttu.edu

http://www.depts.ttu.edu/chemistry/Faculty/Dauria/

 

Principal Research Interests

Tropane alkaloids represent a major class of plant-derived secondary metabolites known to occur in the Solanaceae family but are also present in the families Convolvulaceae, Proteaceae, Rhizophoraceae and Erythroxylaceae. The core defining structure of tropane alkaloids is an 8-azabicyclo[3.2.1] octane nucleus. The diversity of tropane alkaloids is achieved by elaboration of this core through different types of modifications. The genus Erythroxylum (family Erythroxylaceae) contains approximately 230 species with ranges spread throughout the tropics including South America and Madagascar.

Erythroxylum coca and Erythroxylum novogranatense are the most widely used species for the production of cocaine. Very little is known as to the biological and ecological roles that cocaine and other tropane alkaloids play in plants. Their anti-cholinergic properties argue strongly in favour of deterrent activity against herbivores. We have begun molecular and biochemical studies in order to elucidate the biochemical steps which lead to the production of tropane alkaloids in E. coca plants.

 
  Biochemistry and Evolution of Tropane Alkaloid Biosynthesis

The terminal step in the production of cocaine or other tropane related esters is thought to be the formation of the acyl ester via the action of an acyltransferase enzyme. In the case of cocaine, this acyltransferase utilizes the substrates methylecgonine and benzoyl CoenzymeA to produce cocaine and free CoA. I have been working for several years on a plant specific family of acyltransferases commonly referred to as the BAHD acyltransferases. Thus far, more than 8 BAHD acyltransferases have been isolated from Erythroxylum coca (E. coca). Recent results show one of these BAHD members exhibits cocaine synthase activity. Members of my group have successfully developed an LC-MS based ‘realtime’ enzyme assay for cocaine synthase in order to obtain very accurate kinetic data for characterization studies. We are also using antibodies made against the whole purified protein in order to perform immunoprecipitation and immunohistochemical studies.

In addition to the study of the role of acyltransferases in E. coca, I am also actively pursuing what enzymes are involved in forming the first and second rings of the tropane core. Most theories to date suggest that the precursor compound is most likely the mono-methylated polyamine putrescine. With the aid of Dr. Christin Fellenberg, a postdoctoral fellow in my lab we are characterizing the properties of several polyamine synthases that are similar to putrescine methyltransferase and spermine/spermidine synthases. We are also interested in the origins of the benzoic acid portion of cocaine and are combining all of our tools that we have thus far developed for E. coca to develop this system as a model for benzoic acid biosynthesis.

 

Representative Publications