Cynthia K. Holland

Cynthia Holland

Assistant Professor of Biology

413-597-2746
Thompson Biology Lab
At Williams since January of 2020

Education

Ph.D. Washington University, Biology

Areas of Expertise

Protein Biochemistry & Plant Metabolism

Scholarship/Creative Work

About half of all modern pharmaceuticals are derived from or inspired by compounds found in nature, yet the biosynthetic pathways for many natural products remain unknown. These pathways generally use basic metabolic building blocks, like amino acids, as starting materials, which have also been largely under-investigated in plants. Research questions in the Holland laboratory focus on the evolution of enzyme function and regulation in amino acid metabolism and natural product biosynthesis in plants.

Cardenolide biosynthesis in wallflower

Cardenolides are a chemically diverse group of natural products that act as allosteric inhibitors of Na+,K+-ATPase, an essential membrane ion transporter that is found in almost all animal cells. The pharmaceutical cardenolide digoxin is used to treat heart arrhythmias and is on the World Health Organization’s list of essential medicines, but the cardenolide biosynthetic pathway has yet to be investigated. Using a recently published genome for a cardenolide-producing species of wallflower (Erysimum cheiranthoides), our current efforts are focused on identifying and characterizing candidate genes using genomics, protein biochemistry, and analytical chemistry techniques.

Tryptophan metabolism

Tryptophan-derived natural products and intermediates in tryptophan biosynthesis are used as flavoring agents (like the flavor of grape and bitter flavors in horseradish and mustard), fragrances, herbivore repellants, dyes, and cancer drugs, but very little is known about the substrate specificity and regulation of tryptophan biosynthesis in plants. While humans and animals must obtain tryptophan from their diet, plants and bacteria synthesize tryptophan using a 5-step, 7-enzyme pathway. We are currently characterizing the enzymes involved in tryptophan metabolism in Arabidopsis, maize, and citrus using a combination of protein engineering, biochemistry, and plant genetics techniques.

 

Selected publications:

Züst T, Strickler SR, Powell AF, Mabry ME, An H, Mirzaei M, York T, Holland CK, Kumar P, Erb M, Petschenka G, Gómez J-M, Perfectti F, Müller C, Pires JC, Mueller LA, Jander G (2020) Independent evolution of ancestral and novel defenses in a genus of toxic plants (Erysimum, Brassicaceae). eLife 9:e51712

Holland CK, Westfall CS, Schaffer JE, De Santiago A, Zubieta C, Alvarez S, Jez JM (2019) Brassicaceae-specific Gretchen Hagen 3 acyl acid amido synthetases conjugate amino acids to chorismate, a precursor of aromatic amino acids and salicylic acid.  J Biol Chem 294, 16855-64

Holland CK, Berkovich DA, Kohn ML, Maeda H, Jez JM (2018) Structural basis for substrate recognition and inhibition of prephenate aminotransferase from Arabidopsis.  Plant J 94, 304-14

Kroll K*, Holland CK*, Starks CM, Jez JM (2017) Evolution of allosteric regulation in chorismate mutases from early plants.  Biochem J 474, 3705-17. *Equal contribution

Schenck CA*, Holland CK*Schneider MR, Men Y, Lee SG, Jez JM, Maeda HA (2017) Molecular basis of the evolution of alternative tyrosine biosynthesis pathways in plants.  Nature Chem Biol 13, 1029-35. *Equal contribution

Current Committees

  • British Post Graduate Advisory Committee