The Blasticidin S Biosynthesis Gene Cluster from <i>Streptomyces griseochromogenes</i>: Sequence Analysis, Organization, and Initial Characterization

Cone, Martha C.; Yin, Xinhua; Grochowski, Laura L.; Parker, Morgan R.; Zabriskie, T. Mark

doi:10.1002/cbic.200300583

Cited by 58 publications

(54 citation statements)

References 58 publications

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“…Another pair of homologous counterparts for two antibiotics is BlsL/ArgL, both of which show clear similarity to guanidino methyltransferase from Solanum lycopersicum. This methylation is proposed to occur immediately following the leucylation of the ␤-amino group to yield LBS in the BS biosynthesis pathway (9). Accordingly, we propose that ArgL may catalyze the methylation of the guanidyl group in a similar way.…”

Section: Resultsmentioning

confidence: 85%

“…Arginomycin, blasticidin S, and mildiomycin share the core moiety cytosylglucuronic acid (CGA), which is catalyzed by the CGA synthase (BlsD/MilC) via coupling of the UDP-glucuronic acid and free cytosine or its analog (see Fig. S1A in the supplemental material) (9,10). Degenerate primers SCR-For and -Rev (Table S1) were designed based on the multiple DNA sequence alignments with milC, blsD, and other homologous genes from the database (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, oxidoreductase or dehydrogenase counterparts are lacking from both of two gene clusters. A single oxidoreductase, BlsS, that is essential for BS biosynthesis (9) was postulated to govern this step; GouA in gougerotin is an arabinose dehydrogenase-like protein with little homology to BlsS that was proposed to be in charge of the oxidation of 4=-hydroxyl CGA (14). In contrast, no oxidoreductase/dehydrogenase gene(s) can be identified in either the arginomycin or the mildiomycin biosynthetic gene cluster.…”

Section: Resultsmentioning

confidence: 99%

“…With respect to the attachment of ␤-methylarginine to the 4=-amino group of the hexose via an atypical amide bond, ArgJ (a homolog of BlsI encoding a putative ligase) and ArgK (a homolog of BlsK bearing homology to lysyl-tRNA synthetase) might be related. Both blsI and blsK are essential to BS biosynthesis (9), which involves the formation of two amide bonds. As leucylblasticidin S (LBS) was proved to be the penultimate compound in the blasticidin S biosynthetic pathway (12), two enzymes were required to activate and attach leucine and ␤-arginine/or leucyl-␤-arginine to BS.…”

Section: Resultsmentioning

confidence: 99%

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Biosynthesis of the β-Methylarginine Residue of Peptidyl Nucleoside Arginomycin in Streptomyces arginensis NRRL 15941

Feng

Gao

et al. 2014

Appl Environ Microbiol

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bThe peptidyl nucleoside arginomycin is active against Gram-positive bacteria and fungi but displays much lower toxicity to mice than its analog blasticidin S. It features a rare amino acid, ␤-methylarginine, which is attached to the deoxyhexose moiety via a 4=-aminoacyl bond. We here report cloning of the complete biosynthetic gene cluster for arginomycin from Streptomyces arginensis NRRL 15941. Among the 14 putative essential open reading frames, argM, encoding an aspartate aminotransferase (AAT), and adjacent argN, encoding an S-adenosyl methionine (SAM)-dependent methyltransferase, are coupled to catalyze arginine and yield ␤-methylarginine in Escherichia coli. Purified ArgM can transfer the ␣-amino group of L-arginine to ␣-ketoglutaric acid to give glutamate and thereby converts L-arginine to 5-guanidino-2-oxopentanoic acid, which is methylated at the C-3 position by ArgN to form 5-guanidino-3-methyl-2-oxopentanoic acid. Iteratively, ArgM specifically catalyzes transamination from the donor L-aspartate to the resulting 5-guanidino-3-methyl-2-oxopentanoic acid, generating ␤-methylarginine. The complete and concise biosynthetic pathway for the rare and bioactive amino acid revealed by this study may pave the way for the production of ␤-methylarginine either by enzymatic conversion or by engineered living cells.A rginomycin (Fig. 1) is a peptidyl nucleoside antibiotic isolated from Streptomyces arginensis NRRL 15941 that shows bioactivity against Gram-positive bacteria and fungi, such as Micrococcus luteus and Penicillium oxalicum (1). Although the overall skeleton of arginomycin is highly similar to that of blasticidin S (BS) (Fig. 1), a representative peptidyl nucleoside antibiotic exhibiting strong inhibitory activity against rice blast caused by Pyricularia oryzae Cavara (2), arginomycin showed much lower toxicity to mice (1). They differ from each other only in the modification of the L-arginine-derived guanidino side chain (Fig. 1). A feeding experiment indicated that ␤-arginine in BS is derived from an intramolecular amino migration of ␣-arginine (3). BlsG, an arginine 2,3-aminomutase homologous to lysine 2,3-aminomutase (4), was assumed to govern this migration in the BS biosynthesis pathway. In contrast, ␦-N-methylation was demonstrated to be the ultrabiosynthetic step, as the conversion of demethylblasticidin S to BS was observed in a cell extract of the BS producer Streptomyces griseochromogenes supplied with radiolabeled S-adenosyl-L-methionine (SAM) (5). Likewise, ␦-N-methylation of the guanidyl group of arginomycin should also occur after attachment of the guanidino side chain to the nucleoside core moiety. In addition to this, arginomycin bears at the relatively unreactive ␤ position of arginine the ␤-methylarginine moiety for which ␤-methylation is a commitment step and is of considerable interest to this study in uncovering new enzymology. There are two possibilities for the timing of the ␤-methylation of arginine: (i) L-arginine is first converted to free ␤-methylarginine and is coupled with ...

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Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Biosynthesis of the β-Methylarginine Residue of Peptidyl Nucleoside Arginomycin in Streptomyces arginensis NRRL 15941

Feng

Gao

et al. 2014

Appl Environ Microbiol

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“…Interestingly, A54145 belongs to the same class of antibiotics as the CDAs from S. coelicolor that are cyclic lipopeptides active against gram-positive pathogens. In addition, absA-like operons are also found in the biosynthetic gene cluster for blasticidin S, cinnamycin, and enduracidin in Streptomyces griseochromogenes, S. cinnamoneus, and S. fungicidicus, respectively (14,51,53). A unifying feature among the AbsA1-like sensor kinases is their predicted atypical transmembrane topologies.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated AbsA2 Negatively Regulates Antibiotic Production inStreptomyces coelicolorthrough Interactions with Pathway-Specific Regulatory Gene Promoters

McKenzie

Nodwell

2007

J Bacteriol

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The AbsA two-component signal transduction system, comprised of the sensor kinase AbsA1 and the response regulator AbsA2, acts as a negative regulator of antibiotic production in Streptomyces coelicolor, for which the phosphorylated form of AbsA2 (AbsA2ϳP) is the agent of repression. In this study, we used chromatin immunoprecipitation to show that AbsA2 binds the promoter regions of actII-ORF4, cdaR, and redZ, which encode pathway-specific activators for actinorhodin, calcium-dependent antibiotic, and undecylprodigiosin, respectively. We confirm that these interactions also occur in vitro and that the binding of AbsA2 to each gene is enhanced by phosphorylation. Induced expression of actII-ORF4 and redZ in the hyperrepressive absA1 mutant (C542) brought about pathway-specific restoration of actinorhodin and undecylprodigiosin production, respectively. Our results suggest that AbsA2ϳP interacts with as many as four sites in the region that includes the actII-ORF4 promoter. These data suggest that AbsA2ϳP inhibits antibiotic production by directly interfering with the expression of pathway-specific regulators of antibiotic biosynthetic gene clusters.

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Radical Enzymes

Golding

2012

Encyclopedia of Radicals in Chemistry, Biology and Materials

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Radical enzymes catalyze reactions with intermediate radicals, which are not free but bound to the enzyme. The catalytic reactions comprise generation of a radical species that initiates formation of the substrate‐derived radical, followed by conversion to the product‐related radical, and either recycling or decomposition of the initiating radical with release of the product. These characteristics are illustrated with specific radical enzymes. Ribonucleotide reductases (RNRs) use a thiyl radical to enable a common reaction mechanism for the reduction of ribose. There are three classes of RNRs that differ in the manner of thiyl radical generation: use of coenzyme B 12 , S ‐adenosylmethionine (SAM), or dioxygen with bi‐transition metal centers. Coenzyme B 12 ‐dependent eliminases and mutases are like SAM radical enzymes in that they apply the same 5′‐deoxyadenosyl radical as initiating radical, which is also used by coenzyme B 12 ‐ or SAM‐dependent RNRs. The SAM radical enzymes, which multiply in number, are involved in the maturation of enzymes and transfer of ribonucleic acids, as well as in the biosynthesis of many vitamins, coenzymes, and antibiotics. The 2‐ and 4‐hydroxyacyl‐coenzyme A (CoA) dehydratases contain a [4Fe–4S] cluster and utilize intermediate ketyl radicals, which are formed either by reduction or by combined oxidation/deprotonation of the substrates. Similar radical species participate in the reduction of benzoyl‐CoA and other aromatic compounds as well as in photolyases that repair DNA. Finally, flavin radical enzymes and two [4Fe–4S] cluster enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are described. In conclusion, biotechnological applications and evolutionary aspects are discussed.

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The Blasticidin S Biosynthesis Gene Cluster from Streptomyces griseochromogenes: Sequence Analysis, Organization, and Initial Characterization

Cited by 58 publications

References 58 publications

Biosynthesis of the β-Methylarginine Residue of Peptidyl Nucleoside Arginomycin in Streptomyces arginensis NRRL 15941

Biosynthesis of the β-Methylarginine Residue of Peptidyl Nucleoside Arginomycin in Streptomyces arginensis NRRL 15941

Phosphorylated AbsA2 Negatively Regulates Antibiotic Production inStreptomyces coelicolorthrough Interactions with Pathway-Specific Regulatory Gene Promoters

Radical Enzymes

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