title: Inorganic phosphate is a trigger factor for Microbispora sp. ATCC-PTA-5024 growth and NAI-107 production.
abstract: BACKGROUND
  NAI-107, produced by the actinomycete Microbispora sp. ATCC-PTA-5024, is a promising lantibiotic active against Gram-positive bacteria and currently in late preclinical-phase. Lantibiotics (lanthionine-containing antibiotics) are ribosomally synthesized and post-translationally modified peptides (RiPPs), encoded by structural genes as precursor peptides. The biosynthesis of biologically active compounds is developmentally controlled and it depends upon a variety of environmental stimuli and conditions. Inorganic phosphate (Pi) usually negatively regulates biologically-active molecule production in Actinomycetes, while it has been reported to have a positive control on lantibiotic production in Firmicutes strains. So far, no information is available concerning the Pi effect on lantibiotic biosynthesis in Actinomycetes.
  
  
  RESULTS
  After having developed a suitable defined medium, Pi-limiting conditions were established and confirmed by quantitative analysis of polyphosphate accumulation and of expression of selected Pho regulon genes, involved in the Pi-limitation stress response. Then, the effect of Pi on Microbispora growth and NAI-107 biosynthesis was investigated in a defined medium containing increasing Pi amounts. Altogether, our analyses revealed that phosphate is necessary for growth and positively influences both growth and NAI-107 production up to a concentration of 5 mM. Higher Pi concentrations were not found to further stimulate Microbispora growth and NAI-107 production.
  
  
  CONCLUSIONS
  These results, on one hand, enlarge the knowledge on Microbispora physiology, and, on the other one, could be helpful to develop a robust and economically feasible production process of NAI-107 as a drug for human use.
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università degli Studi di Palermo, Viale delle Scienze - Bd. 16, 90128, Palermo, Italy. angia20@inwind.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Giardina
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università degli Studi di Palermo, Viale delle Scienze - Bd. 16, 90128, Palermo, Italy. valeria.alduina@unipa.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Alduina
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università degli Studi di Palermo, Viale delle Scienze - Bd. 16, 90128, Palermo, Italy. giumir@msn.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gallo
authors.affiliation: Naicons S.r.l., Viale Ortles 22/4, 20139, Milan, Italy. pmonciardini@naicons.com.|KtedoGen S.r.l., Viale Ortles 22/4, 20139, Milan, Italy. pmonciardini@naicons.com.
authors.forename: Paolo
authors.initials: P
authors.lastname: Monciardini
authors.affiliation: Naicons S.r.l., Viale Ortles 22/4, 20139, Milan, Italy. msosio@naicons.com.|KtedoGen S.r.l., Viale Ortles 22/4, 20139, Milan, Italy. msosio@naicons.com.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Università degli Studi di Palermo, Viale delle Scienze - Bd. 16, 90128, Palermo, Italy. a.maria.puglia@unipa.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Puglia
mesh_terms: D039903:Actinobacteria / Q000254:growth & development*; D001430:Bacteriocins / Q000096:biosynthesis*; D006801:Humans; D010710:Phosphates / Q000494:pharmacology*
chemical_list: D001430:Bacteriocins; D010710:Phosphates; C528150:microbisporicin