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SUMMARY:Plenary Lecture 6: Metabolic conflicts drive multi-scale organizat
 ion of microbial activities - de Lorenzo\, V (Centro Nacional de Biotecnol
 oga)
DTSTART:20141127T093000Z
DTEND:20141127T100500Z
UID:TALK56389@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:Biological bottlenecks for microbial biodegradation of recalci
 trant compounds in the environment include [i] unfavourable thermodynamics
  of (bio)chemical reactions at stake\, [ii] lack of specificity of existin
 g pathways and enzymes for novel substrates\, and [iii] physicochemical st
 ress encountered in polluted sites. Besides these limitations\, bacterial 
 cells also experience increased endogenous oxidative stress during metabol
 ism of aromatic compounds\, which is exacerbated when enzymes meet subopti
 mal substrates. Evolving bacterial metabolism is thus shaped by chemical c
 onstraints acting on the material and dynamic layout of enzymatic networks
  -and beyond. These are moulded not only for optimisation of given metabol
 ic objectives (e.g. synthesis of a particular amino acid or nucleotide) bu
 t also for curbing the detrimental reactivity of chemical intermediates. T
 hese features suggest that the physical structure of existing biosystems\,
  from operon assemblies to multi-cellular development may ultimately stem 
 from the need to restrain chemical damage and limit the waste inherent to 
 basic metabolic functions. We have examined oxidative stress brought about
  by the still-evolving 2\,4-dinitrotoluene biodegradative pathway in Burkh
 olderia sp. DNT. The dnt pathway of this bacterium apparently evolved from
  a precursor naphthalene degradation route and the first enzyme (2\,4-dini
 trotoluene dioxygenase) maintains some activity towards its earlier substr
 ate. Examination of both in vivo reactions and the associated regulatory s
 ystem suggests that ROS production is the first bottleneck that evolving p
 athways have to overcome for dealing with novel compounds. Evolutionary co
 nsequences -and some hints and genetic tools for engineering multi-strain 
 biocatalysts- will be discussed.\n
LOCATION:Seminar Room 1\, Newton Institute
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