Draft Genome Sequence of
            <i>Streptomyces</i>
            sp. TP-A0356, a Producer of Yatakemycin

Komaki, Hisayuki; Ichikawa, Natsuko; Hosoyama, Akira; Fujita, Nobuyuki; Igarashi, Yasuhiro

doi:10.1128/genomea.01446-15

Cited by 5 publications

(7 citation statements)

References 9 publications

(8 reference statements)

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“…Since orthologs of EndoIV and TatD with high sequence similarity to the E. coli enzymes exist elsewhere in the genome of Streptomyces sp. TP-A0356 48 , the divergent proteins in the YTM producer may have evolved to specifically process AP sites generated from YTMA.…”

Section: Discussionmentioning

confidence: 99%

Toxicity and repair of DNA adducts produced by the natural product yatakemycin

2017

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Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent antimicrobial and antitumor properties and the most recent addition to the CC-1065 and duocarmycin family of natural products. While bulky DNA lesions the size of those produced by YTM are normally removed from the genome by the nucleotide excision repair (NER) pathway, YTM adducts are also a substrate for the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base excision repair (BER) in their elimination. The reason for the extreme toxicity of these lesions and the molecular basis for how they are eliminated by BER have been unclear. Here, we describe the structural and biochemical properties of YTM adducts responsible for their toxicity, and define the mechanism by which they are excised by AlkD. These findings delineate an alternative strategy for repair of bulky DNA damage and establish the cellular utility of this pathway relative to that of NER.

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Section: Discussionmentioning

confidence: 99%

Toxicity and repair of DNA adducts produced by the natural product yatakemycin

2017

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“…11 However, the bhm biosynthetic gene cluster (BGC) has not been identified despite the isolation of 1−3 in 1980 and the recent genome sequencing of alternative BHMs producers. 8,13,19 A typical actinomycete genome contains 20−40 BGCs, and most of them are silent under laboratory culture conditions. 20,21 Ribosome engineering is a rapid and cost-effective strategy to improve the yields of many secondary metabolites or activate silent BGCs.…”

mentioning

confidence: 99%

“…TPA0873 is a known BHMs producer (Tables S5−7). 19 The BhmJ NRPS contains two distinct modules predicted for serine and methyl-proline incorporation (Table S8). 6,18,32 inactivated bhmJ, resulting in a mutant YX3001(ΔbhmJ) without the production of 1−3 (Figure 1B, III; Figure S8).…”

mentioning

confidence: 99%

Activation and Characterization of Bohemamine Biosynthetic Gene Cluster from Streptomyces sp. CB02009

Liu

Sun

et al. 2020

Org. Lett.

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Bohemamines (BHMs) are bacterial alkaloids containing a pyrrolizidine core with two unusual methyl groups. Herein we report the activation of BHMs biosynthesis using a ribosome engineering approach. Characterization of the bhm gene cluster reveals that nonribosomal peptide synthetase BhmJ and Baeyer–Villiger monooxygenase BhmK are responsible for the formation of the pyrrolizidine core, which is further methylated on C-7 by methyltransferase BhmG. The 9-methyl group of BHMs is instead originated from a nonproteinogenic amino acid (2S,5S)-5-methylproline.

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“…In order to probe their functions, we chose AmRox, SaRox, and MsRox, as well as two other Rox homologs: SsRox from Streptomyces sp. TP-A0356 (producer of yatakemycin) (Komaki et al, 2015) and NdRox from Nocardioides dokdonensis (Kwak et al, 2017) to test the Rif-degrading activity (Figure 2A). Their encoding gene sequences were obtained by either direct PCR amplifications or chemical synthesis (Supplementary Table S1).…”

Section: Characterization Of the Rox Proteins From Rifamycin Producers As The Rif Sv-degrading Monooxygenasementioning

confidence: 99%