UAT Professor Distinguishes Himself at UK University

Professor Dr Mansi El-Mansi
Department of Biochemistry, Faculty of Science,
University of Africa (UAT, Bayelsa State, Nigeria

Professor Mansi’s research is focused on metabolic engineering of microorganisms. His wide-ranging experience enables him to employs a multidisciplinary approach in which transcriptomics, proteomics, metabolomics, microbial physiology, and molecular biology as well as bioinformatics are integrated to achieve the set objective.  His research enjoys national and international recognition and, very recently, his proposal for admittance to the DSc degree at the University of Glasgow, Scotland, UK was successful. His DSc title was as follows:

Switches, thresholds, and flux signals in the control of central metabolism’s architecture in Escherichia coli

Switches:        The acetate-diauxic switch
Thresholds:
1. Growth rate (µ) threshold of 0.43h^-1 (±0.02).
2. ATP threshold of 2.14 (±0.04) mmol g^-1 dry weight-h^-1
Flux Signal:    ATP flux through substrate level phosphorylation (SLP) enzymes.

Professor Mansi’s notable achievements in scientific research are as follows:

• At Glasgow University, the author was the first to show that transient increase in the intracellular concentration of isocitrate was a prerequisite for successful adaptation of Escherichia coli to acetate. [El-Mansi et al. 1985].
• At Glasgow University, the author was the first to unravel the interrelationship between pyruvate metabolism and the phosphorylation state of isocitrate dehydrogenase in E. coli. [El-Mansi et al. 1986].
• At Glasgow University, the author was the first to localise and clone the structural gene encoding ICDH kinase/phosphate (aceK) from Escherichia coli ML308 and showed that it was a member of the glyoxylate bypass operon. [El-Mansi et al. 1987].
• At Glasgow University and with the aid of ¹⁴C- radioisotope, the author was the first to unravel how pyruvate flux is partitioned between pyruvate dehydrogenase and PEP synthase. [El-Mansi and Holms, 1989].
• At Glasgow University, the author was the first to characterise the control of carbon flux to acetate excretion and provided three ways through which wasteful flux to acetate excretion can be prevented in industrial process. [El-Mansi and Holms, 1989].
• In collaboration with others, the author was the first to simulate the partition of carbon flux at the junction of isocitrate between ICDH of the Krebs cycle and isocitrate lyase (ICL) of the glyoxylate bypass and showed that ICDH is not rate limiting (controlling) during growth of E. coli on acetate. [El-Mansi, et al. 1994].
• The author was the first to show that the in vivo signal, which triggers the reversible inactivation of ICDH upon adaptation to acetate is not directly related to acetate per se, but rather dependent on the need to maintain high intracellular levels of isocitrate and free HS-CoA. [El-Mansi, 1998].
• The author was the first to show that ICDH is over expressed in the acetate phenotype of E. col, thus providing the first experimental evidence in support of Dan Koshland’s theory of ultrasensitivity. [El-Mansi, 1998].
• The author was the first to argue that acetate and lactate excretions are advantageous to E. coli as it permits a faster growth rate and facilitates the formation of proton gradient, respectively. [El-Mansi, 2004].
• The author was the first to argue that the term “over-flow” metabolism used to describe acetate excretion is an oversimplification of a physiologically significant phenomenon and recommended that it should be re-evaluated and, in turn, abandoned. [El-Mansi, 2004].
• The author was the first to unravel the anaplerotic function of phosphotransacetylase and acetate kinase in replenishing central metabolism with free HS-CoA and ATP, respectively. [El-Mansi, 2004].
• The author was the first to unravel the scientific principles underlying the excretion of ∝-ketoglutarate during the growth of E. coli on acetate as a sole source of carbon under aerobic conditions. [El-Mansi, 2004; El-Mansi et al. 2006].
• In collaboration with others, the author was the first to show that the plasmid-encoded ICDH in Klebsiella pneumoniae is not rate-limiting (controlling) in respect of flux to glutamate excretion as evidenced by a negative flux control coefficient. [El-Mansi et al. 2015].
• In collaboration with others, the author was the first to unravel the scientific principle underlying the ability of Klebsiella Pneumoniae NCTC, CL687/80 to excrete large quantities of glutamate and showed that such excretion is associated with the PC3 indigenous plasmid’s ability to down-regulate the activity of ∝-ketoglutarate dehydrogenase, thus opening the door for the use of regulatory control elements in manipulating fluxes to desirable end products. [El-Mansi et al. 2015].
• In collaboration with others, the author was the first to clone and sequence the plasmid-encoded icd from Klebsiella pneumoniae NCTC, CL687/80  (Gene Bank accession number: BankIt1420989, seq1 HQ822274) and showed that the differences between the plasmid-borne icd and its chromosomally encoded orthologs from other species were negligible. [El-Mansi et al. 2015].
• In collaboration with others, the author was the first to postulate that the expression of the ace operon is under the control of the acetate-diauxic switch, which is triggered in response to a minimum threshold flux signal of ATP. El-Mansi et al. 2021].
• The author was the first to postulate that ATP generated through SLP  may have a different phosphorylation potential to that of the ATP generated via oxidative phosphorylation and further reiterated that different numerical values for the phosphorylation potential enables the organism to direct each pool for different metabolic and regulatory functions. [El-Mansi et al. 2019a].
• The author was the first to propose that the topology of central metabolism of the acetate phenotype of E. coli is bicyclic in nature, and in which the Krebs tricarboxylic acid cycle (TCA) and the dicarboxylic acid (DCA) cycle work in concert with the glyoxylate bypass fulfilling the anaplerotic function [El-Mansi et al. 2019a; El-Mansi et al. 2021].
• In collaboration with others, the author was the first to device a new method for the curing of large indigenous plasmids and successfully deleted several key enzymes including ICDH [El-Mansi et al. 2001].
• The author was the first to show the contrasting effects of ICDH deletion on the partition of carbon fluxes among enzymes of central metabolism in E. coli. [El-Mansi, 2019b].
• In collaboration with others, the author provided metabolic engineering rationales for increasing the efficiency of phenylalanine production in Escherichia coli through constitutive expression of PEP synthase and the application of stoichiometric network analysis [El-Mansi et al. 2019c].
• The author was the first to conceptualise the acetate-diauxic switch as an adaptive sensory “regulatory module” that senses, integrates and transduces specific flux signals to appropriate transcription factors to bring about the expression of the ace operon enzymes (aceBAK) and acetyl CoA synthetase (AcCoA-S) in preparation for adaptation and assimilation of the excreted acetate [El-Mansi, 2019a].
• The author is also the first to postulate that the reversible acetylation of acetyl CoA synthetase and the reversible phosphorylation of isocitrate dehydrogenase in E. coli may be coordinated by the acetate-diauxic switch [El-Mansi, 2019a; El-Mansi et al., 2021].
• Last, but not least, the author has led a panel of internationally recognised academics and industrialists in the production of the highly acclaimed book entitled Fermentation Microbiology and Biotechnology (CRC Taylor and Francis, London, New York). The book, which was first published in 1999 is now in its 4^th edition (2019).

Other achievements that are not pertaining to the argument of this thesis include the following:

• Under the supervision of Dr DJ Hopper, the author was the first to show that the ability of Pseudomonas putida to grow on p-cresol as sole source of carbon was associated with the presence of a large indigenous plasmid and that successive subculturing of the p-cresol phenotype on succinate led to the curing (loss) of the plasmid. [El-Mansi, PhD, thesis UCW, Aberystwyth, UK 1982].
• Under the supervision of Dr DJ Hopper, the author was the first to show that 4-hydroxy- 3-methylabenzoate hydroxylase from Pseudomonas putida is a monooxygenase multi-enzyme complex that is composed of at least two different protein components. While the first was an oxidoreductase (dehydrogenase) type of enzyme, the other component catalysis the hydroxylation reaction [El-Mansi and Hopper, 1989, 1991].