title: Piezotolerance as a metabolic engineering tool for the biosynthesis of natural products.
abstract: Thermodynamically, high-pressure (>10's of MPa) has a potentially vastly superior effect on reactions and their rates within metabolic processes than temperature. Thus, it might be expected that changes in the pressure experienced by living organisms would have effects on the products of their metabolism. To examine the potential for modification of metabolic pathways based on thermodynamic principles we have performed simple molecular dynamics simulations, in vacuo and in aquo on the metabolites synthesized by recombinant polyketide synthases (PKS). We were able to determine, in this in silico study, the volume changes associated with each reaction step along the parallel PKS pathways. Results indicate the importance of explicitly including the solvent in the simulations. Furthermore, the addition of solvent and high pressure reveals that high pressure may have a beneficial effect on certain pathways over others. Thus, the future looks bright for pressure driven novel secondary metabolite discoveries, and their sustained and efficient production via metabolic engineering.
authors.affiliation: Biological and Environmental Systems Group, Department of Chemical and Process Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, UK. p.c.wright@sheffield.ac.uk
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Wright
authors.forename: Robin E
authors.initials: RE
authors.lastname: Westacott
authors.forename: Adam M
authors.initials: AM
authors.lastname: Burja
mesh_terms: D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods*; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000737:chemistry*; D011312:Pressure; D011487:Protein Conformation
chemical_list: D009097:Multienzyme Complexes