Identification of a red pigment from Streptomyces coelicolor A3(2) as a mixture of prodigiosin derivatives.

Tsao, Sheng-Wan; Rudd, Brian A. M.; He, Xian-Guo; Chang, Ching‐Jer; Floss, Heinz G.

doi:10.7164/antibiotics.38.128

Cited by 139 publications

(146 citation statements)

References 19 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…84 One such member of this family was extracted from the pigment of several Streptomyces species in 1975 by the Gerber group using chromatographic techniques, and initially assigned the structure 39 ( Figure 12) using mass spectral, UV-vis, and NMR analysis. 85 A revision of this structure to 40 (Figure 12) came three years later by the same author, 86 though confusion surrounding the correct structure and atropisomeric potential of the natural product remained, 87,88 until relatively recent studies put any ambiguities to rest and confirmed the correct general structure as 40. 89,90 It was in a study by Challis et al in 2010 that NOESY correlations of the HCl salts of extracted streptorubin B allowed for assignment of the major naturally occurring product as being the anticonfiguration with regards to the positioning of the C7ʹ n-butyl group relative to rings A and B, with the syn configuration only present in minor amounts.…”

Section: Streptorubin B: a Recently Synthesized Antibiotic From Red Pmentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

View full text Add to dashboard Cite

. (2015). A twist of nature-the significance of atropisomers in biological systems. Natural Product Reports: a journal of current development in bioorganic chemistry, 32 (11), 1562-1583. A twist of nature-the significance of atropisomers in biological systems AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized. AbstractRecently identified natural atropisomeric compounds with potential medicinal applications are presented. The ability of natural receptors to possess differential binding between atropisomers is an important factor when considering active and inactive atropisomeric drugs, and has required the development of new techniques for atropselective synthesis of desired targets. Advances in this field therefore have significant relevance to modern pharmaceutical and medicinal chemistry. The atropisomeric natural products discussed include hibarimicinone, flavomannins, talaromannins, viriditoxin, rugulotrosin A, abyssomicin C, marinopyrroles, dixiamycins, streptorubin B, ustiloxins A-F, haouamine A, bisnicalaterines, and tedarene B, all of which show significant potential as leads in antibiotic, antiviral and anticancer studies. The importance for the development of common practices regarding atropisomer recognition and classification is also emphasized.

show abstract

Section: Streptorubin B: a Recently Synthesized Antibiotic From Red Pmentioning

confidence: 99%

A twist of nature – the significance of atropisomers in biological systems

2015

View full text Add to dashboard Cite

show abstract

“…This carbapenem is easily detected by a simple plate bioassay employing a sensitive strain of Escherichia coli. In contrast to the more complex situation found in Streptomyces this simple carbapenem appears to be the only antibiotic produced by S. marcescens and E. carotouora, although S. marcescens does also produce the red pigment prodigiosin (Morrison, 1966) which is structurally related to the antibiotic undecylprodigiosin produced by Streptomyces ceolicolor and Streptomyces liuidans (Tsao et al, 1985;Hopwood et al, 1995). Although E. carotouora and S. marcescens both produce the same antibiotic, in S. marcescens carbapenem is produced throughout the growth phase (Bycroft et al, 1988), whereas in E .…”

Section: Introductionmentioning

confidence: 99%

A pheromone-independent CarR protein controls carbapenem antibiotic synthesis in the opportunistic human pathogen Serratia marcescens

et al. 1998

View full text Add to dashboard Cite

Strain ATCC 39006 of Serratia marcescens makes the same carbapenem, (5R)-carbapen-2-em-3-carboxylic acid (Car), as the Erwinia carotovora strain G S l O l .Unlike E. carotovora, where the onset of production occurs in the lateexponential phase of growth in response to the accumulation of the small diffusible pheromone N-(3~oxohexanoyl)-~-homoserine lactone (OHHL), in 5. marcescens carbapenem is produced throughout the growth phase and does not appear to involve any diffusible pheromone molecule. Two cosmids capable of restoring antibiotic production in E. carotovora group I carbapenem mutants were isolated from an 5. marcescens gene library. These cosmids were shown to contain a homologue of the E. carotovora carR gene, encoding a CarR protein with homology to the LuxR family of transcriptional regulators. The S. marcescens carR was subcloned and shown to be capable of complementing in trans, in the absence of OHHL, an E. carotovora carR car/ double mutant, releasing the heterologous E. carotovora host from pheromone dependence for carbapenem production. The apparent OHHL-independence of the S. marcescens CarR explains the constitutive nature of carbapenem production in this strain of 5. marcescens.

show abstract

“…1A) (2)(3)(4)(5). The therapeutic potential of prodiginines was demonstrated in prior studies in which analogues of undecylprodiginine exhibited immunosuppressant activity and analogues of streptorubin B exhibited anticancer activity (6,7).…”

mentioning

confidence: 99%

Structure and Function of the RedJ Protein, a Thioesterase from the Prodiginine Biosynthetic Pathway in Streptomyces coelicolor

Whicher

Florova

Sydor

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Prodiginines are a class of red-pigmented natural products with immunosuppressant, anticancer, and antimalarial activities. Recent studies on prodiginine biosynthesis in Streptomyces coelicolor have elucidated the function of many enzymes within the pathway. However, the function of RedJ, which was predicted to be an editing thioesterase based on sequence similarity, is unknown. We report here the genetic, biochemical, and structural characterization of the redJ gene product. Deletion of redJ in S. coelicolor leads to a 75% decrease in prodiginine production, demonstrating its importance for prodiginine biosynthesis. RedJ exhibits thioesterase activity with selectivity for substrates having long acyl chains and lacking a ␤-carboxyl substituent. The thioesterase has 1000-fold greater catalytic efficiency with substrates linked to an acyl carrier protein (ACP) than with the corresponding CoA thioester substrates. Also, RedJ strongly discriminates against the streptomycete ACP of fatty acid biosynthesis in preference to RedQ, an ACP of the prodiginine pathway. The 2.12 Å resolution crystal structure of RedJ provides insights into the molecular basis for the observed substrate selectivity. A hydrophobic pocket in the active site chamber is positioned to bind long acyl chains, as suggested by a long-chain ligand from the crystallization solution bound in this pocket. The accessibility of the active site is controlled by the position of a highly flexible entrance flap. These data combined with previous studies of prodiginine biosynthesis in S. coelicolor support a novel role for RedJ in facilitating transfer of a dodecanoyl chain from one acyl carrier protein to another en route to the key biosynthetic intermediate 2-undecylpyrrole.Modular polyketide synthases (PKSs) 5 and non-ribosomal peptide synthetases (NRPSs) are large multienzymes that catalyze the production of a wide range of biologically active compounds currently used as therapies for human diseases (1). Most PKSs and NRPSs are organized as assembly lines in which specific enzymatic domains catalyze elongation or modification of specific pathway intermediates. One key difference between these two types of assembly lines is that PKSs use acyl thioesters as substrates, whereas NRPSs use amino acids. Both PKS and NRPS pathway intermediates are tethered, via a thioester bond, to the phosphopantetheine (Ppant) arms of acyl/ peptidyl carrier protein (ACP/PCP) domains throughout chain assembly. Thioester cleavage, most often catalyzed by a terminating or type I thioesterase (TE I), releases the fully assembled polyketide/peptide from the carrier domain.Prodiginine biosynthesis is directed by the red cluster in Streptomyces coelicolor and involves hybrid NRPS/PKS multienzymes employing an ␣-oxoamine synthase (OAS) in a highly unusual chain release mechanism to assemble undecylprodiginine (1) and its carbocyclic derivative streptorubin B (2) (Fig. 1A) (2-5). The therapeutic potential of prodiginines was demonstrated in prior studies in which analogues of undecylprod...

show abstract

Identification of a red pigment from Streptomyces coelicolor A3(2) as a mixture of prodigiosin derivatives.

Cited by 139 publications

References 19 publications

A twist of nature – the significance of atropisomers in biological systems

A twist of nature – the significance of atropisomers in biological systems

A pheromone-independent CarR protein controls carbapenem antibiotic synthesis in the opportunistic human pathogen Serratia marcescens

Structure and Function of the RedJ Protein, a Thioesterase from the Prodiginine Biosynthetic Pathway in Streptomyces coelicolor

Contact Info

Product

Resources

About