GriC and GriD Constitute a Carboxylic Acid Reductase Involved in Grixazone Biosynthesis in Streptomyces griseus

Suzuki, Hirokazu; Ohnishi, Yasuo; Horinouchi, Sueharu

doi:10.1038/ja.2007.52

Cited by 27 publications

(23 citation statements)

References 19 publications

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“…The pair of genes, clmG1 and clmG2, shows high similarity with griC and griD from Streptomyces griseus, genes known to catalyze a carboxylic acid reduction in grixazone biosynthesis (Suzuki et al, 2007). During the third phase of collismycin A biosynthesis, the formation of an intermediate carrying a carboxylic group has been proposed (Garcia et al, 2012) and this intermediate could be a good substrate for ClmG1/ClmG2, reducing the carboxylic group to an aldehyde.…”

Section: Insertional Inactivation Of Genes Involved In Latementioning

confidence: 98%

Engineering the Biosynthesis of the Polyketide-Nonribosomal Peptide Collismycin A for Generation of Analogs with Neuroprotective Activity

García

Vior

González‐Sabín

et al. 2013

Chemistry & Biology

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Collismycin A is a member of the 2,2'-bipyridyl family of natural products that shows cytotoxic activity. Structurally, it belongs to the hybrid polyketides-nonribosomal peptides. After the isolation and characterization of the collismycin A gene cluster, we have used the combination of two different approaches (insertional inactivation and biocatalysis) to increase structural diversity in this natural product class. Twelve collismycin analogs were generated with modifications in the second pyridine ring of collismycin A, thus potentially maintaining biologic activity. None of these analogs showed better cytotoxic activity than the parental collismycin. However, some analogs showed neuroprotective activity and one of them (collismycin H) showed better values for neuroprotection against oxidative stress in a zebrafish model than those of collismycin A. Interestingly, this analog also showed very poor cytotoxic activity, a feature very desirable for a neuroprotectant compound.

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Section: Insertional Inactivation Of Genes Involved In Latementioning

confidence: 98%

Engineering the Biosynthesis of the Polyketide-Nonribosomal Peptide Collismycin A for Generation of Analogs with Neuroprotective Activity

García

Vior

González‐Sabín

et al. 2013

Chemistry & Biology

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“…Mutational analyses of two other on May 11, 2018 by guest http://aac.asm.org/ genes in the thn cluster, thnN and thnO, have revealed that they are absolutely required for thienamycin biosynthesis (25), although their role is still unknown. Based on its similarity to GriC-GriD, a carboxylic acid reductase complex essential for grixazone biosynthesis in Streptomyces griseus, it was proposed previously that ThnN-ThnO may be responsible for the reduction of a carboxylic acid to the corresponding aldehyde in the thienamycin pathway (33). A decarboxylation step occurs during the generation of the cysteaminyl side chain after cysteine incorporation in thienamycin biosynthesis (25,35).…”

Section: Discussionmentioning

confidence: 99%

Mutational Analysis of the Thienamycin Biosynthetic Gene Cluster from Streptomyces cattleya

Rodríguez

Núñez

Braña

et al. 2011

Antimicrob Agents Chemother

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The generation of non-thienamycin-producing mutants with mutations in the thnL, thnN, thnO, and thnI genes within the thn gene cluster from Streptomyces cattleya and their involvement in thienamycin biosynthesis and regulation were previously reported. Four additional mutations were independently generated in the thnP, thnG, thnR, and thnT genes by insertional inactivation. Only the first two genes were found to play a role in thienamycin biosynthesis, since these mutations negatively or positively affect antibiotic production. A mutation of thnP results in the absence of thienamycin production, whereas a 2-to 3-fold increase in thienamycin production was observed for the thnG mutant. On the other hand, mutations in thnR and thnT showed that although these genes were previously reported to participate in this pathway, they seem to be nonessential for thienamycin biosynthesis, as thienamycin production was not affected in these mutants. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) analysis of all available mutants revealed some putative intermediates in the thienamycin biosynthetic pathway. A compound with a mass corresponding to carbapenam-3-carboxylic acid was detected in some of the mutants, suggesting that the assembly of the bicyclic nucleus of thienamycin might proceed in a way analogous to that of the simplest natural carbapenem, 1-carbapen-2-em-3-carboxylic acid biosynthesis. The accumulation of a compound with a mass corresponding to 2,3-dihydrothienamycin in the thnG mutant suggests that it might be the last intermediate in the biosynthetic pathway. These data, together with the establishment of cross-feeding relationships by the cosynthesis analysis of the non-thienamycin-producing mutants, lead to a proposal for some enzymatic steps during thienamycin assembly.

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“…1) [21]. Meanwhile, it has been found that two genes in the grixazone biosynthesis gene cluster constituted a CAR [22]. The substrate profile of an enzyme provides guidance for its synthetic application, but this important information of the known CARs is limited [12,13,23,24].…”

Section: Introductionmentioning

confidence: 99%

Exploring the synthetic applicability of a new carboxylic acid reductase from Segniliparus rotundus DSM 44985

Duan

Yao

Chen

et al. 2015

Journal of Molecular Catalysis B: Enzymatic

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GriC and GriD Constitute a Carboxylic Acid Reductase Involved in Grixazone Biosynthesis in Streptomyces griseus

Cited by 27 publications

References 19 publications

Engineering the Biosynthesis of the Polyketide-Nonribosomal Peptide Collismycin A for Generation of Analogs with Neuroprotective Activity

Engineering the Biosynthesis of the Polyketide-Nonribosomal Peptide Collismycin A for Generation of Analogs with Neuroprotective Activity

Mutational Analysis of the Thienamycin Biosynthetic Gene Cluster from Streptomyces cattleya

Exploring the synthetic applicability of a new carboxylic acid reductase from Segniliparus rotundus DSM 44985

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