Research in the Nikolau Lab focuses on deciphering new knowledge concerning the structure and regulation of metabolic processes providing core capabilities in interdisciplinary initiatives on the Iowa State University campus.

As Director of the Center for Metabolic Biology, Nikolau leads a group of faculty from four departments (Agronomy; Biochemistry, Biophysics and Molecular Biology; Genetics, Development and Cell Biology; and Chemical and Biological Engineering) spanning three colleges (Liberal Arts and Sciences; Agriculture and Life Sciences; Engineering) that forge links between the Plant Sciences Institute and the Bioeconomy Institute. An exclusive component of the Center is the W.M. Keck Metabolomic Research Laboratory, which was established in 2002 by a grant from the W.M. Keck Foundation; the laboratory provides ISU researchers with unique capabilities for analyzing metabolism.

Forging these collaborations has led to the establishment of the NSF-funded Engineering Research Center for Biorenewable Chemicals (CBiRC) and the NIH-funded Center for Research on Botanical Dietary Supplements. 

  • Acetyl-CoA is a metabolite that sits at a key point connecting catabolic and anabolic metabolism, and it is also juxtaposed between central carbon metabolism and specialized metabolism. Because of the unique central metabolic position that acetyl-CoA occupies, flux through this intermediate is highly regulated by the integration of a variety of different mechanisms. Plants generate and utilize different pools of acetyl-CoA for the biosynthesis of a variety of phytochemicals, many of which represent the most reduced forms of carbon (i.e., they are the most energy-dense compounds) that biological systems can produce, namely, oils, hydrocarbons, waxes, and terpenoids.

  • The recent explosion in genome data was made possible by 20-years of advances in analytical chemistry, which increased the cost-efficiencies of DNA sequencing technologies.  Similar technological advances are now required to more efficiently characterize the functionality of an organism’s genetic potential.  The Nikolau group is developing metabolomics as a functional genomics tool to decipher metabolic and physiological functions of genes of unknown function.

  • Biotin is a water-soluble vitamin that is biosynthesized by plants, and some bacteria and fungi.  One of its biochemical functions is as a covalently-bound cofactor on a family of enzymes that catalyze reactions in a variety of crucial metabolic processes. Examples of such enzymes are acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and geranoyl-CoA carboxylase, which are required for lipogenesis, amino acid metabolism and isoprenoid metabolism.

  • Enzymes are the workhorses of metabolism, catalyzing chemical transformations that would otherwise be very slow.  Enzymes therefore offer many biotechnological applications in the chemical and food industries.  The Nikolau group has focused on key enzyme systems that have applications in the emerging biorenewable chemical industry. The goals of this research is to two-fold: 1) understand the structure-function relationship of these enzymes systems so as to improve their biotechnological applications; and 2) incorporate novel enzyme systems into appropriate hosts to bioengineer novel metabolic products.  This research is focused on the following enzyme systems:

  • Simple hydrocarbons (e.g. n-alkanes and n-alkenes), that are at the chemical level identical to currently used gasoline and diesel fuels, occur discreetly in biological systems. Some algae and photosynthetic microbial systems accumulate simple hydrocarbons in large quantities as a means of storing carbon and energy.  Other organisms, such as plants and insects produce these compounds as part of the cuticle, which acts as a water barrier at the interface between the organism and the environment.

  • Metabolomics is the science of determining the metabolome of a biological sample. The metabolome is the collection of low molecular weight organic molecules associated with a biological sample, which are not direct products of genetic information (as defined by the central dogma). These organic molecules directly interact with macromolecules (usually enzymes), which themselves are products of genetic information, and these interactions may or may not lead to chemical transformations.

  • The term “specialized metabolism” encompasses metabolic processes that are asymmetrically distributed across phylogenetic space - historically this metabolism was called secondary metabolism.  In contrast to central metabolism, which is common to all life forms, specialized metabolism generates the “chemical-spice” of different life forms, and thus is responsible for the large degree of chemical diversity in the biosphere.