Zoom seminar for OIST "Discovery of an anti-metabolon: a paradoxical way of regulating enzymes"


Wednesday, June 29, 2022 - 15:30 to 16:30






Dr. Vijay Jayaraman / Weizmann Institute of Science



3.5 billion years of biochemical evolution on earth has given rise to complex life forms including us. This wouldn’t have been possible without enzyme-driven metabolic processes. While the catalytic function of enzymes is key for various cellular processes, equally important is the regulation of an enzyme function. An enzyme’s activity can be regulated in many different ways: binding of an allosteric regulator, post-translational modifications, and change in oligomeric state to name some.


In my talk, I will present a novel mode of enzyme regulation that we discovered in B. subtilis. The enzyme of interest GudB, that breaks glutamate, is regulated by binding to another enzyme, GltAB that catalyzes the opposite reaction. I will present kinetic and structural evidence that in the GudB-GltAB anti-metabolon, GudB is inhibited by GltAB binding. Why to inhibit an enzyme in such a complex way? It turns out that this complex mode of regulation is an elegant solution for the metabolic requirements of the interior and the peripheral cells of the Bacillus biofilm. I will also briefly present other examples of such designs in biology (made of opposing activities) and discuss their utility in synthetic biology. Finally, I will conclude with an evolutionary perspective of the emergence of this complex in the Bacillus species tree and describe our efforts to evolve an anti-metabolon using directed evolution.


Biosketch: Vijay Jayaraman is a post-doctoral fellow in the lab Prof. Uri Alon at the Weizmann Institute of Science, Israel. Currently, he is working on deciphering design principles of phosphorylation based regulation of proteins. Before joining Uri’s lab he worked with late Prof. Dan Tawfik on aspects related to evolution of enzyme regulation and oligomeric states. Vijay has a Bachelor’s degree in pharmaceutical chemistry and a Master’s degree in Biotechnology. For his Ph.D. dissertation, he worked on the structural and functional aspects of the enzyme fumarate hydratase from Plasmodium falciparum and Methanocaldococcus jannaschii.


Sponsor or Contact

Mika Uehara RUA of the Laurino Unit (mika.uehara@oist.jp)


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