Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

Hu, Dennis X.; Withall, David M.; Challis, Gregory L.; Thomson, Regan J.

doi:10.1021/acs.chemrev.6b00024

Cited by 150 publications

(149 citation statements)

References 165 publications

(527 reference statements)

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“…25 In fact, nonylprodigiosin and its cyclic derivatives isolated from BRA 177 are structurally related to undecylprodigiosin and the only difference detected is that the hydrocarbon moiety is 2 methylene shorter. 25 In agreement with the chemical structure, multilocus sequence analysis (MLSA) performed with the amino acid sequences of eight protein homologs encoded on undecylprodigiosin red and prodigiosin pig clusters, and involved in biosynthesis the MBC precursor (RedWIOMNYV/ PigAFGHIKM) and precursors condensation (RedH/PigC), separated gram-negative prodiginiosin producers from actinobacteria undecylprodigiosin-related prodiginine producers in two main clades. 26 Therefore, the enzymology codified on the detected contig NODE_44 is in agreement with that expected for the biosynthesis of nonylprodigiosin and derivatives.…”

Section: Genome Miningmentioning

confidence: 99%

“…25,[27][28][29] BLASTx searches using the amino acid sequence of Red/Mar proteins missed by the ANTISMASH screening as query against the genome of BRA 177 recovered an additional 31.335 bp contig (NODE_60) containing the respective red (mar) gene homologs clustered ( Figure 4, Table 1). Therefore, the genome mining strongly supports that contigs NODE_44 and NODE_60 gene composition includes BRA 177 putative prodiginine BGC, named from now on as the non cluster ( Figure 4).…”

Section: Genome Miningmentioning

confidence: 99%

“…These proteins selectively interact with the fatty acyl thioester tethered to RedQ (acyl carrier protein, ACP), which, in turn, is generated at the beginning of the 2-undecylpyrrole biosynthetic pathway by action of RedP (FabH-like betaketoacyl-acyl carrier protein synthase III), RedR (FabF-like beta-ketoacyl-acyl carrier protein synthase II), and RedQ combined with the full reduction set of FAS enzymology, ketoreductase (KR), dehydratase (DH) and enoylreductase (ER). 25 RedJ thioesterase is proposed to hydrolyze dodecanoyl-RedQ generating the dodecanoic acid. Then, RedL_A would activate and attach the dodecanoyl acid to RedL first acyl carrier protein domain (RedL_ACP 1 ) by a thioester linkage.…”

Section: Genome Miningmentioning

confidence: 99%

“…3, 2017 recently reviewed. 25 In fact, nonylprodigiosin and its cyclic derivatives isolated from BRA 177 are structurally related to undecylprodigiosin and the only difference detected is that the hydrocarbon moiety is 2 methylene shorter. …”

mentioning

confidence: 99%

“…25,31 In this case, RedJ would not have the fine capability to discriminate between the two long chain substrates, and RedL_A would be the key component for selecting decanoyl substrate on the prodiginine biosynthetic pathway of Actinomadura spp.…”

mentioning

confidence: 99%

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Bioprospecting Anticancer Compounds from the Marine-Derived Actinobacteria Actinomadura sp. Collected at the Saint Peter and Saint Paul Archipelago (Brazil)

Silva¹,

Guimarães²,

Ferreira³

et al. 2016

J. Braz. Chem. Soc.

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The actinomycete strain BRA 177 was recovered from sediment samples collected at the St. Peter and St. Paul Archipelago, Brazil. This work accessed the ability of this strain, identified as Actinomadura sp., to produce bioactive metabolites by exploring the genome and characterizing chemistry and cytotoxicity of isolated compounds. From the crude ethyl acetate extract, the pigments nonylprodigiosin, cyclononylprodigiosin and methylcyclooctilprodigiosin were isolated and displayed cytotoxicity against human tumor and non-tumor cell lines. Sequencing, assembling and prospection of BRA 177 draft genome led to identification of two contigs encoding enzymes with high homology to those from prodiginine biosynthetic gene clusters (BGC) in actinomycetes. Further, Actinomadura sp. BGC presented unique putatives RedJ thioesterase and RedL-like type I PKS, involved on selection of prodiginine biosynthetic fatty acyl precursor, and RedG-like Rieske oxygenase, key for cyclization of the prodiginines, suggesting that cyclononilprodigiosin and methylcyclooctylprodigiosin could actually be considered chemical signatures of Actinomadura spp.Keywords: cytotoxicity, genome mining, marine microorganisms, marine natural products, prodiginine derivatives IntroductionThe St. Peter and St. Paul Archipelago (SPSPA) is a remote group of islets located off the Brazilian coast. It is a rare case of geological formation, as this is the single portion of the Atlantic Ocean where the mantle has surfaced, permeating an area just about 17,000 m 2 above sea level.1 Peripheral habitats such as SPSPA and surroundings are a potential source of marine biodiversity with high degree of endemism. [1][2][3][4] Microbial diversity studies, however, are still very scarce, 5 while the biotechnological potential of microorganisms has only recently been described by our group in a preliminary assessment of the chemical diversity and prospection of anticancer compounds in extracts derived from culturable actinobacteria recovered from sediments collected therein. 6 Essentially, this work showed a high incidence of bioactive extracts among those obtained from the 268 isolates, and dereplication studies demonstrated the Bioprospecting Anticancer Compounds from the Marine-Derived Actinobacteria Actinomadura sp.J. Braz. Chem. Soc. 466 presence of notorious bioactive compounds, such as, but not restricted to, staurosporines, piericidins, saliniketals and rifamycins. Such preliminary results merely hinted on the biological and metabolic diversity that is predicted for the SPSPA. In this scenario, the strain, thereby coded as BRA 177, showed remarkable cytotoxicity against a human tumor cell line, 6 and was, thus, bidden for broader investigations. In fact, traditional bioprospective efforts have long merged chemical studies and biological assays in search for functional natural products. While these well-used equipment and methodologies have been ever evolving into more sensitive and high-throughput analytical tools, for the past decade or so, another perspectiv...

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Section: Genome Miningmentioning

confidence: 99%

Section: Genome Miningmentioning

confidence: 99%

Section: Genome Miningmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Bioprospecting Anticancer Compounds from the Marine-Derived Actinobacteria Actinomadura sp. Collected at the Saint Peter and Saint Paul Archipelago (Brazil)

Silva¹,

Guimarães²,

Ferreira³

et al. 2016

J. Braz. Chem. Soc.

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The Catalytic Enantioselective Stetter Reaction

Flanigan¹,

Ozboya²,

Tanpure³

et al. 2021

Organic Reactions

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The catalytic enantioselective Stetter reaction is the coupling of an aldehyde with an electron‐deficient alkene via the conjugate addition of an acyl anion equivalent (Breslow intermediate) generated from the aldehyde and a chiral N ‐heterocyclic carbene (NHC) catalyst. The process affords 1,4‐dicarbonyl compounds and related systems, such as β‐nitroketones, in an efficient and atom‐economical fashion and with generally good‐to‐excellent enantioselectivities when fused polycyclic chiral triazolylidenes are employed as the NHC catalysts. The scope of the transformation is particularly broad for intramolecular reactions, but in the case of the intermolecular variant, only certain types of aldehyde donors and electrophilic alkenes can be successfully coupled together. This chapter describes theoretical and operational aspects of the catalytic enantioselective Stetter reaction such that the reader will be able to obtain optimal results in their own research. A detailed mechanistic overview is included to account for the factors that influence stereoselectivity and yield, and results from experimental and computational mechanistic studies are summarized. In addition, catalyst synthesis, reaction variants, applications in target‐directed synthesis, and comparison to other methods for generating 1,4‐dicarbonyl compounds are also presented. Tabular surveys are organized according to the modality of reactivity, either intra‐ or intermolecular, and the type of aldehyde donor. The literature is covered from the first disclosure of a catalytic enantioselective Stetter reaction in 1996 through to the end of 2019.

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