Top: (Top row) Sensitivity of S. coelicolor mutants to GlcNAc. Spores (5 × 105 CFU) of S. coelicolor M145 and its mutant derivatives ∆nagB, SMA11, ∆nagB∆nagS, ∆nagB∆nagSC (∆nagB∆nagS expressing nagS) and ∆nagB∆nagSE (∆nagB∆nagS with empty plasmid pSET152) were streaked on MM agar plates with 1% mannitol (Mann) and 1% mannitol plus 10 mM GlcNAc (GlcNAc). (Bottom row) NagS and its role in GlcNAc sensing. Spores of M145 and ∆nagS were plated on MM and R5 with 0, 0.001, 0.01, 0.1, 1, 5, 10, 20, 50, 100, 150, and 200 mM GlcNAc. Note that nagS mutants hardly respond to GlcNAc. Bottom: Model for the metabolic control of development by GlcNAc and NagS. During late vegetative growth of streptomycetes, the old vegetative or substrate hyphae are degraded in a process of programmed cell death (PCD), to produce the nutrients required to build the aerial mycelium (see mycelial drawings on the right). Mycelial lysis results in breakdown of the cell-wall, leading to the accumulation of GlcNAc-6P, which is a major nutritional signal for the onset of development and antibiotic production. NagS converts GlcNAc-6P into 6P-chromogen I (denoted as X-Ac-6P), which in turn is deacetylated by NagA into a toxic metabolite (denoted as X-6P) that resembles ribose. The toxic metabolite promotes cell lysis, thus releasing more GlcNAc-6P that serves as substrate for NagS and NagA. A salvage pathway then switches off the toxic pathway again. For this, GlcNAc-6P is converted by NagA and NagB into Fructose-6P (Fru-6P), which enters the pentose phosphate pathway (PPP), thereby producing 6-phosphogluconate (6-PG), a metabolic inhibitor of NagS. Thus, production of toxic metabolites ceases and the transition to aerial growth can be initiated. Arrows with round ends represent inhibition, dashed arrow shows proposed activity.
GlcNAc build-up acts as a key metabolic signal in #Streptomyces, but how does it triggers developmental responses? @gillesvanwezel.bsky.social &co show that the enzyme NagS dehydrates GlcNAc-6P into a reactive intermediate, triggering a toxicity-based checkpoint @plosbiology.org 🧪 plos.io/44pE08I
