The biosynthesis, biochemistry and physiology of coenzyme 3PG-F420
Coenzymes promote productive enzymatic activities assisting in almost all major metabolic pathways. Coenzyme F420 is a deazaflavin that acts as a hydride carrier in diverse redox reactions and has been indicated in a range of both bacteria and archaea. 3PG -F420 is a novel hydroxylated derivative of coenzyme F420, found in the Gram-negative, endofungal bacterium Paraburkholderia rhizoxinica, a symbiont of phytopathogenic fungi Rhizopus microsporus.
The availability of the exotic cofactor F420 is not generous and the biosynthetic pathway of F420 has remained elusive regarding the starting precursor and substrate specificity of key enzymes involved. 2-phospho-L-lactate guanylyltransferase (CofC in Archaea and also known as FbiD in Bacteria) is a key enzyme in the biosynthesis of coenzyme F420. Within the field of research, both 2-phospho-L-lactate (2-PL) and phosphoenolpyruvate (PEP) have been recognized as the accepted substrates by CofC/FbiD of Archaea and Mycobacteria respectively. In contrast, CofC of P. rhizoxinica accepts 3-D-phosphoglyceric acid (3-PG) as a substrate thus leading to the formation of a novel derivative termed coenzyme 3PG-F420. Both 3-PG and PEP are intermediate of glycolysis while availability, source and function of 2-PL are yet to be determined.
The main goals of the thesis are to complete our model of 3PG-F420 biosynthesis, to discover more 3PG-F420 producing organisms and to study the biochemical and physiological roles of 3PG-F420 in these organisms.
(2022) Diversification by CofC and Control by CofD Govern Biosynthesis and Evolution of Coenzyme F420 and Its Derivative 3PG-F420. mBio , e0350121.
(2020) Redox Coenzyme F 420 Biosynthesis in Thermomicrobia Involves Reduction by Stand-Alone Nitroreductase Superfamily Enzymes Appl Environ Microbiol 86(12), e00457-20.
(2019) Metabolic Pathway Rerouting in Paraburkholderia rhizoxinica Evolved Long-Overlooked Derivatives of Coenzyme F420. ACS Chem Biol 14(9), 2088-2094.
Start of PhD
December 1, 2019