Phosphoinositides are involved in control of the glucose-dependent growth resumption that follows the transition phase in Streptomyces lividans

The interruption of the sbl4 gene of Streptomyces lividans was previously shown to lead to relief of glucose repression of the normally strongly glucose-repressed (x-amylase gene. In addition to this relief, an early entry into stationary phase was observed when cells were grown in a minimal medium containing glucose as the main carbon source. In this study, we established that this mutant does not resume growth after the transition phase when cultured in the complex glucose-rich liquid medium R2YE and sporulates much earlier than the wild-type strain when plated on solid R2YE. These phenotypic differences, which were abolished when glucose was omitted from the R2YE medium, correlated with a reduced glucose uptake ability of the sbl4 mutant strain. sbl4 was shown to encode a bifunctional enzyme possessing phospholipase C-like and phosphoinositide phosphatase activities. The cleavage of phosphoinositides by SblA seems necessary to trigger the glucose-dependent renewed growth that follows the transition phase. The transient expression of sbl4 that takes place just before the transition phase is consistent with a regulatory role for this gene during the late stages of growth. The tight temporal control of sbl4 expression was shown to depend on two operator sites. One, located just upstream of the -35 promoter region, likely constitutes a repressor binding site. The other, located 170 bp downstream of the GTG sbl4 translational start codon, may be involved in the regulation of the degradation of the sbl4 transcript. This study suggests that phosphoinositides constitute important regulatory molecules in Streptomyces, as they do in eukaryotes.