Izvorni znanstveni članak
Identification of Lipstatin-Producing Ability in Streptomyces virginiae CBS 314.55 Using Dereplication Approach
Gordan Sladič
; Krka d.d., Novo mesto, Šmarješka cesta 6, SI-8501 Novo Mesto, Slovenia
Matilda Urukalo
; University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia
Matjaž Kirn
; Krka d.d., Novo mesto, Šmarješka cesta 6, SI-8501 Novo Mesto, Slovenia
Urška Lešnik
; Acies Bio d.o.o., Tehnološki park 21, SI-1000 Ljubljana, Slovenia
Vasilka Magdevska
; Acies Bio d.o.o., Tehnološki park 21, SI-1000 Ljubljana, Slovenia
Neda Benički
; Krka d.d., Novo mesto, Šmarješka cesta 6, SI-8501 Novo Mesto, Slovenia
Mitja Pelko
; Krka d.d., Novo mesto, Šmarješka cesta 6, SI-8501 Novo Mesto, Slovenia
Aleš Gasparič
; Krka d.d., Novo mesto, Šmarješka cesta 6, SI-8501 Novo Mesto, Slovenia
Peter Raspor
; University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia
Tomaž Polak
; University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia
Štefan Fujs
; Acies Bio d.o.o., Tehnološki park 21, SI-1000 Ljubljana, Slovenia
Paul A. Hoskisson
; Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Hamnett Wing, 161 Cathedral Street, Glasgow, G4 0RE, UK
Hrvoje Petković
; University of Ljubljana, Biotechnical Faculty, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia
Sažetak
Streptomyces species are prolific producers of bioactive metabolites, such as β-lactone-containing lipstatin produced by Streptomyces toxytricini, an intermediate used in semi-synthetic process for production of anti-obesity drug orlistat. Understanding the distribution of identical or structurally similar molecules produced by a taxonomic group is of particular importance when trying to isolate novel biologically active compounds or strains producing known metabolites of medical importance with potentially improved properties. Until now, only two independent isolates of S. toxytricini species have been known to be producers of lipstatin. According to the current taxonomic criteria, S. toxytricini belongs to Streptomyces lavendulae phenotypic cluster. Taxonomy-based dereplication approach coupled
with in vitro assay was applied to screen the S. lavendulae phenotypic cluster for production of lipstatin-like lipase inhibitors using synthetic p-nitrophenol derivatives of C4 and C16 lipids. Screening the available strains from public collections belonging to S. lavendulae phenotypic cluster, high lipase inhibitory activity was identified in the Streptomyces virginiae CBS 314.55 culture supernatants. HPLC and LC-MS/MS confirmed lipstatin production
by a new Streptomyces species for the first time. We have demonstrated that the new lipstatin-producing strain S. virginiae morphologically and physiologically differs from S. toxytricini substantially; however, the production capacity of the newly identified lipstatin-producing species S. virginiae is comparable to S. toxytricini. We have thus demonstrated the effectiveness of a simple and affordable dereplication approach for identification of potentially novel and useful industrial strains available in public culture collections.
Ključne riječi
lipstatin; Streptomyces virginiae; dereplication; lipase inhibitor
Hrčak ID:
126171
URI
Datum izdavanja:
15.9.2014.
Posjeta: 2.107 *