Deciphering the Biosynthesis Pathway of the Antitumor Thiocoraline from a Marine Actinomycete and Its Expression in Two <i>Streptomyces</i> Species

Lombó, Felipe; Velasco, Ana; Castro, Angelina Ramos; Calle, Fernando de la; Braña, Alfredo F.; Sánchez-Puelles, José María; Méndez, Cármen; Salas, José A.

doi:10.1002/cbic.200500325

Cited by 167 publications

(182 citation statements)

References 68 publications

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“…Successful incorporation of (2S,3S)-[6¢-2 H]-3-hydroxy-L-tryptophan (3a) supported the intermediacy of 3, indicating that b-hydroxylation of tryptophan involves covalent attachment to L-tryptophan to the ACP domain of the non-ribosomal peptide synthetase (Ecm13), hydroxylation with cytochrome P-450 monooxygenase (Ecm12), and release of the hydroxylated product by the thioesterase (Ecm2), 12 as in the case of tyrosine (novobiocin) 16 and histidine (nikkomycin). 17 Recently, four gene clusters of quinomycin-type antibiotics (Figure 1, 1, 2, triostin A and thiocoraline) have been identified, 6,9,14,15 all of which share four homologous genes (identity %) (ecm2/trsB/swb14/tioQ (65-75%), ecm11/trsC/swb10/tioF (30-72%), ecm12/trsB/swb13/tioI (64-80%), and ecm13/trsR/swb11/tioK (58-76%)), which were proposed to be responsible for chromophore biosynthesis. Although the clusters of 1 and triostin A consist of homologous genes ecm3/trsP (80%) and ecm4/trsO (72%) probably responsible for QXC biosynthesis, 6 the clusters of 2 and thiocoraline have alternative unique genes swb1/tioG (57%) and swb2/tioH (58%) probably involved in HQA biosynthesis, 9 as shown in Scheme 1.…”

Section: Bioinformatics Analysis Of Quinomycin Family Antibioticsmentioning

confidence: 99%

“…These results indicated that 5 is an intermediate in the biosynthesis of 8. In a previous study of the biosynthesis of thiocoraline, Salas and colleagues 15 proposed that kynurenine (9) derived from L-tryptophan with TioF (L-tryptophan-2,3-dioxygenase) and TioL (arylformamidase) is an intermediate that is further transformed with TioH (oxidoreductase) and TioI (cytochrome P-450 monooxygenase) to HQA 8. Tsodikova and colleagues 18 reported functional analysis of TioF, which converted tryptophan to 9, supporting the intermediacy of 9.…”

Section: Cloning Expression and Purification Of Swb1 And Swb2mentioning

confidence: 99%

“…Among more than 20 congeners of this class of antibiotics, only two major chromophoresquinoxaline-2-carboxylic acid (QXC, 6) and 3-hydroxyquinaldic acid (HQA, 8)-have been identified (Scheme 1). 5 Although biosynthetic studies of these chromophores have been performed for 1 11,12 and triostin 13 and several gene clusters have been reported, 6,9,14,15 little experimental data were obtained. Here, we report chromophore biosynthesis from L-tryptophan by unique pathway switching through the common intermediate (2S, 3R)-3-hydroxy-L-kynurenine (5).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics

et al. 2010

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Quinomycin antibiotics, represented by echinomycin, are an important class of antitumor antibiotics. We have recently succeeded in identification of biosynthetic gene clusters of echinomycin and SW-163D, and have achieved heterologous production of echinomycin in Escherichia coil. In addition, we have engineered echinomycin nonribosomal peptide synthetase (NRPS) to generate echinomycin derivatives. However, the biosynthetic pathways of intercalative chromophores quinoxaline-2-carboxylic acid (QXC) and 3-hydroxyquinaldic acid (HQA), which are important for biological activity, were not fully elucidated. Here, we report experiments involving incorporation of a putative advanced precursor, (2S, 3R)-[6'-2H]-3-hydroxy-L-kynurenine, and functional analysis of the enzymes Swb1 and Swb2 responsible for late-stage biosynthesis of HQA. Based on these experimental results, we propose biosynthetic pathways for both QXC and HQA via the common intermediate 3-hydroxy-L-kynurenine

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Section: Bioinformatics Analysis Of Quinomycin Family Antibioticsmentioning

confidence: 99%

Section: Cloning Expression and Purification Of Swb1 And Swb2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics

et al. 2010

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“…Since environmental conditions of the sea are extremely different from terrestrial conditions, they produce different types of antibiotics. Several antibiotics have been isolated from marine actinobacteria by many researchers [20][21][22][23][24][25][26][27][28][29][30] . The isolated antibiotics are entirely new and unique when compared to those from the terrestrial ones 31 .…”

Section: Biotechnological Importance Of Marine Actinobacteriamentioning

confidence: 99%

Research on marine actinobacteria in India

et al. 2007

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Marine actinobacteriology is one of the major emerging areas of research in tropics. Marine actinobacteria occur on the sediments and in water and also other biomass (mangrove) and substrates (animal). These organisms are gaining importance not only for their taxonomic and ecological perspectives, but also for their unique metabolites and enzymes. Many earlier studies on these organisms were confi ned only to the temperate regions. In tropical environment, investigations on them have gained importance only in the last two decades. So far, from the Indian peninsula, 41 species of actinobacteria belonging to 8 genera have been recorded. The genus, Streptomyces of marine origin has been more frequently recorded. Of 9 maritime states of India, only 4 have been extensively covered for the study of marine actinobacteria. Most of the studies conducted pertain to isolation, identifi cation and maintenance of these organisms in different culture media. Further, attention has been focused on studying their antagonistic properties against different pathogens. Their biotechnological potentials are yet to be fully explored.

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“…identified that is NRPS genes showed similarity (>90%) to Streptomyces albus J1074, a strain commonly used as an expression host. 216,217 This similarity prompted us to investigate previous natural products reported from…”

Section: Streptomyces Sp (Cmb-cs038) and Streptomyces Albus J1074mentioning

confidence: 99%

Microbial biodiscovery: Exploring venomous animal associated microbes as sources of new chemical diversity

Iniguez¹

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Microorganisms produce a large number of medically relevant small molecules through unique biosynthetic mechanisms. These small molecules have been widely used to develop drugs to treat a range of infectious diseases, cancers and other pathologies. In their natural environment microorganisms use these small molecules for signalling or defence. As microorganisms have adapted to different environments, they have greatly expanded their chemical profile and thus the investigation of microorganisms from new environments has often led to the discovery of novel chemistry.Microbes often exist in association with higher eukaryotic hosts and are therefore exposed to unique environments and thus produce unique chemistry. The host organism can benefit by utilising microbial metabolites for their own defence against infections, predators, and for chemical signalling. Interestingly, some venomous animals such as puffer fish and the blue ringed octopus utilise toxins produced by associated microbes to defend against predators. However this chemistry remains largely unexplored for the vast majority of venomous animals. In this study, we investigated metabolites from microbes associated with venomous animals including spiders, centipedes, cone snails, scorpions and wasps.We cultivated microbes from 15 venomous animals to produce a library of ~360 strains. The Chapter 1 Reviews the current status of drug discovery and symbiotic microbial strains involved in producing bioactive metabolites Poster.

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Deciphering the Biosynthesis Pathway of the Antitumor Thiocoraline from a Marine Actinomycete and Its Expression in Two Streptomyces Species

Cited by 167 publications

References 68 publications

Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics

Involvement of common intermediate 3-hydroxy-L-kynurenine in chromophore biosynthesis of quinomycin family antibiotics

Research on marine actinobacteria in India

Microbial biodiscovery: Exploring venomous animal associated microbes as sources of new chemical diversity

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