In recent years significant progress has been made in elucidating the
regulation of carbohydrate metabolism in Lactococcus lactis and other
lactic acid bacteria. Since insight in these mechanisms could provide
valuable tools for metabolic engineering, an overview of the various g
lobal control systems in Gram-positive bacteria is presented with spec
ific attention for inducer exclusion, inducer expulsion and catabolite
repression. Inducer exclusion is the phenomenon where the addition of
a rapidly metabolizable sugar like glucose to the medium results in a
reduced uptake of other sugars. Under the same circumstances another
system called inducer expulsion is active that reduces the intracellul
ar concentration of sugar phosphates by dephosphorylating sugar phosph
ates and removing the sugars from the cell. Both mechanisms have been
shown to depend on the phosphorylation state of residue serine 46 of t
he phosphocarrier HPr by a metabolite-activated kinase. Apart from all
osteric control, the carbohydrate metabolism can also be regulated at
the transcriptional level. An example of transcriptional regulation is
catabolite repression where the presence of a rapidly metabolizable s
ugar in the medium reduces the transcription of genes required for the
utilization of other sugars. Gram-positive bacteria mediate catabolit
e repression via a transcriptional regulator, CcpA. To analyze the rol
e of HPr and CcpA in the sugar metabolism in Lactococcus lactis, the g
enes encoding HPr and CcpA, ptsH and ccpA respectively, have been clon
ed and analyzed. (C) Inra/Elsevier, Paris.