CS-11-4 - The thiamin thiazole synthase THI4 as a target for synthetic biology

Monday, July 16
2:03 PM - 2:23 PM

The metabolic cost of protein turnover and other maintenance processes amounts to about 25% of the carbon and energy captured by crops through photosynthesis. Optimizing the scale and efficiency of these maintenance processes could increase the amount of carbon and energy available to generate biomass. Although this strategy for boosting bioproductivity has potential, it has been largely eclipsed by its inverse, the ever-popular ‘increase carbon gain by maximizing photosynthesis’ strategy. This is because of the difficulty in selecting targets for engineering and synthetic biology to drive carbon loss down, and the relative ease in selecting targets to drive carbon gain up.

This bottleneck in selecting ‘carbon loss’ targets may soon be alleviated. Advances in mass spectrometry-based proteomics now allow measurement of individual protein turnover rates. These measurements show that the thiamin synthesis enzyme THI4 is turned over faster than any other protein in barley and Arabidopsis. Bioenergetic calculations show that the energy consumed by THI4 turnover may account for up to 5% of maintenance costs, or roughly 1% of all carbon fixed by photosynthesis. Therefore, replacing THI4 with a more efficient enzyme could free up substantial carbon for use in growth.

Plant THI4s are short-lived because they are suicide enzymes, i.e. catalyze just one reaction, which irreversibly inactivates them. The inactivation occurs because THI4 destroys an active-site cysteine residue to obtain the sulfur atom needed to make thiamin. Intriguingly, a few anaerobic prokaryotes have THI4s that lack an active site cysteine and use sulfide as a sulfur donor, making them efficient catalysts. Intriguingly, certain plants contain – besides a canonical THI4 – a THI4 isoform lacking an active-site cysteine. Various aerobic prokaryotes likewise contain cysteine-less THI4s. We show that some of these THI4s can complement E. coli and yeast thiamin auxotrophs. Synthetic biology could potentially replace wasteful canonical THI4s with such enzymes.



Jaya Joshi – University of Florida; Andrew Hanson – University of Florida

Guillaume AW Beaudoin, PhD

Postdoctoral Associate
University of Florida

Guillaume Beaudoin is currently a post-doctoral associate in Dr. Andrew Hanson’s lab at the University of Florida. He obtained his undergraduate degree at Concordia University in Montreal, QC and his PhD in plant biochemistry at the University of Calgary. He has expertise in microbiology, metabolic biochemistry, organic chemistry and mass spectrometry. His current research interests include: (i) application of metabolite damage and repair to improve synthetic biology platforms and (ii) the use of synthetic biology to improve wasteful processes in plants.


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CS-11-4 - The thiamin thiazole synthase THI4 as a target for synthetic biology

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