Muscroft-Taylor, Andrew C.


Publications (1)

Genetic drift and genome reduction in the plant pathogenCandidatusLiberibacter solanacearum shapes a new enzyme in lysine biosynthesis

Citation
Gilkes et al. [posted content, 2023]
Names (1)
“Liberibacter solanacearum”
Abstract
AbstractThe effect of population bottlenecks and genome reduction on enzyme function is poorly understood. ‘CandidatusLiberibacter solanacearum’ is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid—a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the effects of genome reduction and genetic drift on the function ofCa. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyses the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate thatCLsoDHDPS is expressed inCa. L. solanacearum and expression is increased ∼2-fold in the insect host compared toin planta.CLsoDHDPS has increased aggregation propensity, implying mutations have destabilised the enzyme but are compensated for through elevated chaperone expression and a stabilised oligomeric state.CLsoDHDPS uses a ternary-complex kinetic mechanism, which is unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure ofCLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study reveals the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary association. We suggest that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.