Differential regulation of undecylprodigiosin biosynthesis in the yeast-scavenging Streptomyces strain MBK6

Abstract

Streptomyces are efficient chemists with a capacity to generate diverse and potent chemical scaffolds. The secondary metabolism of these soil-dwelling prokaryotes is stimulated upon interaction with other microbes in their complex ecosystem. We observed such an interaction when a Streptomyces isolate was cultivated in a media supplemented with dead yeast cells. Whole-genome analysis revealed that Streptomyces sp. MBK6 harbours the red cluster that is cryptic under normal environmental conditions. An interactive culture of MBK6 with dead yeast triggered the production of the red pigments metacycloprodigiosin and undecylprodigiosin. Streptomyces sp. MBK6 scavenges dead-yeast cells and preferentially grows in aggregates of sequestered yeasts within its mycelial network. We identified that the activation depends on the cluster-situated regulator, mbkZ, which may act as a cross-regulator. Cloning of this master regulator mbkZ in S. coelicolor with a constitutive promoter and promoter-deprived conditions generated different production levels of the red pigments. These surprising results were further validated by DNA-protein binding assays. The presence of the red cluster in Streptomyces sp. MBK6 provides a vivid example of horizontal gene transfer of an entire metabolic pathway followed by differential adaptation to a new environment through mutations in the receiver domain of the key regulatory protein MbkZ.

Anti-Melanogenic Activity of Undecylprodigiosin, a Red Pigment Isolated from a Marine Streptomyces sp. SNA-077

“…2, 22.8, 28.4, 29.2, 29.4-29.7, 32.0, 58.9, 93.7, 112.3, 112.7, 116.6, 118.8, 128.7, 130.1, and 171.6. Based on interpretation of the MS and 1D NMR spectroscopic data and comparison of the NMR data to previous reports (Bikash et al, 2021), compound 1 was identified as undecylprodigiosin.…”

“…The NMR spectrum of compound 1 displayed proton signals at δ H 7.28 (1H), 7.01 (s, 1H), 6.97 (1H), 6.85 (1H), 6.37 (1H), 6.21 (1H), 6.10 (s, 1H), 4.02 (s, 3H, O-CH3), 2.79 (s, 2H), 1.21-1.26 (m, 20H), and 0.86 (s, 3H) and carbons at δ C 14.2, 22.8, 28.4, 29.2, 29.4-29.7, 32.0, 58.9, 93.7, 112.3, 112.7, 116.6, 118.8, 128.7, 130.1, and 171.6. Based on interpretation of the MS and 1D NMR spectroscopic data and comparison of the NMR data to previous reports ( Bikash et al ., 2021 ), compound 1 was identified as undecylprodigiosin.…”

“…Undecylprodigiosin, a well-studied bioactive compound ( Tsao et al ., 1985 ; Malpartida et al ., 1990 ), is produced by specific microorganisms, particularly certain strains of Streptomyces bacteria. This compound has been thoroughly investigated for its potential therapeutic properties, including antitumor, immunosuppressant, antifungal, and antimalarial activities ( Stankovic et al ., 2014 ; Bikash et al ., 2021 ). This comprehensive examination of prodigiosin’s performance across diverse applications provides robust support for its potential as a versatile and valuable compound in the fields of medicine, biotechnology, and cosmetics.…”

Resourcefulness of propylprodigiosin isolated from Brevundimonas olei strain RUN-D1

“…Propylprodigiosin-producing bacteria have not been reported to the best of our knowledge, and we are yet to lay our hands on a report on prodigiosin-producing Brevidomonas olei . However, literature has suggested different derivatives of prodigiosin such as prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), undecylprodigiosin metacycloprodigiosin, streptorubin B, and cycloprodigiosin (Bikash et al 2021 ; Habash et al 2020 ).…”

Physical interactions triggerStreptomycesto prey on yeast using natural products and lytic enzymes

“…Close physical contact and environmental signals between microorganisms in the soil microbiome have been shown to initiate cascades of reactions that elicit the production of secondary metabolites 11,12 . Indeed, direct physical contact between various Streptomyces species and several microorganisms stimulates Streptomyces to produce undecylprodigiosins 13,14 . Gamma-butyrolactones and even select antibiotics are important chemical signals for intraspecies communication and regulation of gene expression in Streptomyces 6 .…”