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- Title
Inorganic phosphate is a trigger factor for Microbispora sp. ATCC-PTA-5024 growth and NAI- 107 production.
- Authors
Giardina, Anna; Alduina, Rosa; Gallo, Giuseppe; Monciardini, Paolo; Sosio, Margherita; Puglia, Anna Maria
- Abstract
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 posttranslationally 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. Conclusion 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.
- Subjects
PHOSPHATES; ACTINOMYCETALES; PEPTIDES; LANTIBIOTICS; GRAM-positive bacteria; POLYPHOSPHATES
- Publication
Microbial Cell Factories, 2014, Vol 13, Issue 1, p1
- ISSN
1475-2859
- Publication type
Article
- DOI
10.1186/s12934-014-0133-0