AmfS, an Extracellular Peptidic Morphogen in Streptomyces griseus

Abstract

The amf gene cluster was previously identified as a regulator for the onset of aerial-mycelium formation in Streptomyces griseus. The nucleotide sequences of amf and its counterparts in other species revealed a conserved gene organization consisting of five open reading frames. A nonsense mutation in amfS, encoding a 43-aminoacid peptide, caused significant blocking of aerial-mycelium formation and streptomycin production, suggesting its role as a regulatory molecule. Extracellular-complementation tests for the aerial-mycelium-deficient phenotype of the amfS mutant demonstrated that AmfS was secreted by the wild-type strain. A null mutation in amfBA, encoding HlyB-like membrane translocators, abolished the extracellular AmfS activity without affecting the wild-type morphology, which suggests that AmfBA is involved not in production but in export of AmfS. A synthetic C-terminal octapeptide partially induced aerial-mycelium formation in the amfS mutant, which suggests that an AmfS derivative, but not AmfS itself, serves as an extracellular morphogen.

Developmental Regulation of theStreptomyces lividans ramGenes: Involvement of RamR in Regulation of theramCSABOperon

“…RamR has often been suggested to play a role in the regulation of ramCSAB (16,22,37). The dependence of the ramCSAB genes on ramR has been demonstrated by complementation experiments.…”

“…This cluster consists of genes encoding a sensor kinase (RamC), a small protein (RamS), the components of an ABC transporter (RamAB), and a response regulator (RamR) (16,22). Homologous gene clusters have been identified in S. griseus (amf) and Streptomyces avermitilis (36,37). Involvement of the ram genes in development has been demonstrated by both the accelerated development observed after this gene cluster was introduced as a single extra copy or on a multicopy plasmid into S. lividans and the negative effects on differentiation when disrupted.…”

“…Recently, Ueda and coworkers demonstrated that the C-terminal part of AmfS partially restores the development of an amfS mutant when supplied exogenously. This led to the proposal of a model in which AmfA and -B are involved in the export and processing of AmfS, which functions as an extracellular signaling molecule (37). Additional experiments will be required to reveal the function of the ram gene products and the relationship to formation of aerial hyphae.…”

Dual Transcriptional Control of amfTSBA , Which Regulates the Onset of Cellular Differentiation in Streptomyces griseus

“…Our previous study strongly suggested that AmfS acts as an extracellular morphogenic peptide that stimulates aerial growth (27). The AmfS precursor peptide expressed in substrate mycelium may be modified by an unknown mechanism and secreted by AmfA and AmfB to induce aerial growth.…”

“…We studied the regulatory role and function of the amf gene cluster in the onset of morphological development in S. griseus (25)(26)(27). The gene cluster consists of five coding sequences encoding a probable transmembrane protein (AmfT), a probable secreted peptide (AmfS), two HlyB-type ABC transporters (AmfB and AmfA), and a response regulator of a twocomponent regulatory system (AmfR) (Fig.…”