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This review attempts to provide a rational explanation for microbial metabolite over-production, a phenomenon manifest with many wild-type and mutant organisms. After analysing the relationships between catabolic and anabolic processes within the growing cell (which point to the presence of sufficient kinetic control elements to ensure a stringent coupling between the two), consideration is given to mechanisms that might allow the rate of catabolism to be varied independently of the rate of anabolism. It is in this latter context that an excretion of specific metabolites appears to play a key role.

Bacillus stearothermophilus grew readily on glycerol in carbon-limited chemostat culture and expressed a high carbon conversion efficiency. However, the strain of organism used (probably B. stearothermophilus var. nondiastaticus) proved particularly sensitive to glycerol, both respiration and growth being severely impeded by any surfeit of this compound. Sensitivity was found to correlate with an exceptionally high level of expression of glycerol kinase [activities of more than 80 mumol min-1 (mg protein)-1 were manifest in crude cell-free extracts], coupled with low activities of methylglyoxal synthase and of glyoxylase (enzymes of the methylglyoxal bypass). It is proposed that metabolic dysfunction results from an uncontrolled gross accumulation of glycerol phosphate (and early products of its metabolism) within the cells, coupled with depletion of the intracellular phosphate pool.

Glucose-limited cultures of Klebsiella aerogenes NCTC 418 (and the supposedly identical strain NCIB 418) possessed a glucose phosphoenolpyruvate (PEP) phosphotransferase activity that varied markedly and progressively with growth rate, from more than 250 nmol min-1 (mg dry wt cells)-1 at D = 0.1 h-1 to less than 100 nmol min-1 (mg dry wt cells)-1 at D = 0.8 h-1. When relieved of the glucose limitation, substrate was used at a rate that bore no precise relationship to the cells' phosphotransferase activity. Similarly, glucose-sufficient (phosphate- or potassium-limited) cultures metabolized glucose at high rates, whereas the cells possessed only moderate glucose PEP phosphotransferase activities. These results are compared with those reported for glucose-limited cultures of Escherichia coli and for variously limited cultures of K. aerogenes. Glucose-sufficient cultures, as well as glucose-limited cultures that had been temporarily relieved of glucose limitation, excreted partially oxidized products of glucose catabolism in considerable amounts. The relevance of this 'overflow' metabolism to studies of glucose transport using [U-14C]glucose is emphasized.

The regulation of the PQQ-linked glucose dehydrogenase in different organisms is reviewed. It is concluded that this enzyme functions as an auxiliary energy-generating mechanism, because it is maximally synthesized under conditions of energy stress. It is now definitively established that the oxidation of glucose to gluconate generates metabolically useful energy. The magnitude of the contribution of the oxidation of glucose to gluconate via this enzyme to the growth yield of organisms such as Acinetobacter calcoaceticus is not yet clear.

The biomass concentration extant in potassium-limited cultures of either Klebsiella pneumoniae or Bacillus stearothermophilus (when growing at a fixed temperature and dilution rate in a glucose/ammonium salts medium) increased progressively as the medium pH value was raised step-wise from 7.0 to 8.5. Because the macromolecular composition of the organisms did not vary significantly, this increase in biomass could not be attributed to an accumulation of storage-type polymers but appeared to reflect a pH-dependent decrease in the cells' minimum K+ requirement. Significantly, this effect of pH was not evident with cultures in which no ammonium salts were present and in which either glutamate or nitrate was added as the sole nitrogen source; however, it was again manifest when various concentrations of NH4Cl were added to the glutamate-containing medium. This suggested a functional replacement of K+ by NH4+, a proposition consistent with the close similarity of the ionic radii of the potassium ion (1.33 A) and the ammonium ion (1.43 A). At pH 8.0, and with a medium containing both glutamate (30 mM) and NH4Cl (100 mM), cultures of B. stearothermophilus would grow without added potassium at a maximum rate of 0.7 h-1. Under these conditions the cells contained maximally 0.1% (w/w) potassium (derived from contaminating amounts of this element in the medium constituents), a value which should be compared with one of 1.4% (w/w) for cells growing in a potassium-limited medium containing initially 0.5 mM K+.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Mg(2+)-limited Bacillus subtilis var. niger, growing in a chemostat in a simple salts medium, contained considerably more potassium and phosphorus than Mg(2+)-limited Aerobacter aerogenes growing in a similar medium at corresponding dilution rates. 2. Growth of the bacillus in a K(+)-limited environment did not lower the cellular potassium and phosphorus contents, the molar proportions of cell-bound magnesium, potassium, RNA (as nucleotide) and phosphorus being approximately constant at 1:13:5:13 (compared with 1:4:5:8 in Mg(2+)-limited or K(+)-limited A. aerogenes). 3. Growth of B. subtilis in a phosphate-limited environment caused the cellular phosphorus content to be lowered to a value similar to that of Mg(2+)-limited A. aerogenes, but the potassium content was not correspondingly lowered; the molar potassium:magnesium ratio varied from 14 to 17 with changes in dilution rate from 0.4 to 0.1hr.(-1). 4. Whereas over 70% of the cell-bound phosphorus of Mg(2+)-limited or K(+)-limited A. aerogenes was contained in the nucleic acids, these polymers accounted for less than 50% of the phosphorus present in similarly limited B. subtilis; much phosphorus was present in the walls of the bacilli, bound in a teichoic acid-type compound composed of glycerol phosphate and glucose (but no alanine). 5. Phosphate-limited B. subtilis cell walls (from organisms grown at a dilution rate of 0.2hr.(-1)) contained little phosphorus and no detectable amounts of teichoic acid, but 40% of the cell-wall dry weight could be accounted for by a teichuronic acid-type compound; this contained a glucuronic acid and galactosamine, neither of which could be detected in the walls of Mg(2+)-limited B. subtilis grown at a corresponding rate. 6. It is suggested that the high concentration of potassium in growing B. subtilis (compared with A. aerogenes) results from the presence of large amounts of anionic polymer (teichoic acid or teichuronic acid) in the bacillus cell walls.