Identification of a Novel Bioactive Phenazine Derivative and Regulation ofphoPon Its Production inStreptomyces lomondensisS015

Abstract

Natural phenazines are a class of multifunctional secondary metabolites of bacteria that play an important role in the biocontrol of plant pathogens. In this paper, a novel bioactive phenazine derivative was isolated from Streptomyces lomondensis S015 through silica gel chromatography and preparative high-performance liquid chromatography (HPLC). The structure was identified as 1-carboxyl-6-formyl-4,7,9-trihydroxy-phenazine (CFTHP) by NMR spectroscopy in combination with ultraperformance liquid chromatography & mass spectrometry (UPLC-MS). CFTHP could inhibit Pythium ultimum, Rhizoctonia solani, Septoria steviae, and Fusarium oxysporum f. sp. niveum with minimal inhibitory concentration (MIC) values of 16, 32, 16, and 16 μg/mL, respectively. A global regulatory gene phoP could positively regulate CFTHP biosynthesis since its production was 3.0-fold enhanced by phoP overexpression and inhibited by phoP deletion in Streptomyces lomondensis S015. These studies illustrated the potential of CFTHP as a promising biopesticide and provided a reference for phenazine production improvement.

Advances in Phenazines over the Past Decade: Review of Their Pharmacological Activities, Mechanisms of Action, Biosynthetic Pathways and Synthetic Strategies

“…Niveum, with MIC values of 16 µg/mL, 32 µg/mL, 16 µg/mL and 16 µg/mL, respectively. These biological data showed the potency of 43 as a promising hit for the further development as a biopesticide [48]. Cha et al isolated compounds 44 and 45 (Figure 7) from Streptomyces sp.…”

“…Here, synthetic phenazine derivatives will be classified into the following categories in detail, with the perspective of biological activities and functional groups connected to phenazine core. According to related reports, bacterium would stop growth in MIC of 2-4 µg/mL and die in MIC of 2 µg/mL [48]. Halogenated phenazines derivatives are tested as antibacterial agents which could target multiple persistent bacterial phenotypes effectively and show negligible toxicity against mammalian cells.…”

Enhanced Biosynthesis of Phenazine-1,6-dicarboxylic Acid in Streptomyces coelicolor

“…Resulted in PDC Production. S. lomondensis S015 has been reported to produce PDC derivatives such as lomofungin while the production of PCA and its derivatives were not detected, 17,52 which suggests that the core phenazine BGC from S015 strain is favorable for PDC production. However, the genetic engineering system of the S015 strain was not well established.…”

Development of Artificial Synthetic Pathway of Endophenazines in Pseudomonas chlororaphis P3

“…During the fermentation process, 1 mL culture broth was taken every 12 h until 72 h. The extraction method of phenazine derivatives was consistent with that described by Deng et al [32]. The mobile phase was 1‰ formic acid water and methanol.…”