Actinorhodin production is markedly enhanced when an acidic pH
shock is applied to a surface-grown culture of Streptomyces coelicolor A3(2). For an in-depth study of this phenomenon, transcriptional analyses using
DNA microarrays and reverse transcription polymerase chain reaction and proteomic analysis were performed. Investigated were expression levels of the regulators and
enzymes responsible for signal transduction and
actinorhodin biosynthesis and
enzymes involved in some major metabolic pathways. Regulators PkaG, AfsR, AfsS and/or another unidentified regulator and ActII-ORF4, in sequence, were observed to be activated by pH
shock. In addition, a number of genes associated with
actinorhodin production and secretion and the major central metabolic pathways investigated were observed to be upregulated with pH
shock.
Fatty acid degradation was particularly promoted by pH
shock, while
fatty acid biosynthesis was suppressed; it is envisaged that this enriches the precursor pool (
acetyl-CoA) and building blocks for
actinorhodin biosynthesis. Furthermore,
glucose 6-phosphate
dehydrogenases, initiating the pentose phosphate pathway, were highly activated by pH
shock, enriching the reduced
nicotinamide adenine dinucleotide phosphate (
NADPH) pool for biosynthesis in general. It is deduced that these metabolic changes caused by pH
shock have positively contributed to the stimulation of
actinorhodin biosynthesis in a concerted manner.