Cloning, Characterization and Heterologous Expression  of the Indolocarbazole Biosynthetic Gene Cluster from Marine-Derived Streptomyces sanyensis FMA

Li, Tong; Du, Yuanyuan; Cui, Qiu; Zhang, Jingtao; Zhu, Weiming; Hong, Kui; Li, Wenli

doi:10.3390/md11020466

Cited by 33 publications

(23 citation statements)

References 36 publications

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“…In silico analysis of the annotated genome of Streptomyces sp. MA37 using antiSMASH 3.0 [37] identified one putative bec biosynthetic gene cluster (BGC) likely to be involved in the production of BE-13793C 1, showing high homology to rebeccamycin (AB071405.1) [32,38], staurosporine (AB088119.1) [39][40][41][42], K252a (FJ031030) [43], and AT2433 (DQ297453) [44] BGCs.…”

Section: Proposed Biosynthetic Pathwaymentioning

confidence: 99%

A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite

et al. 2020

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Whole-genome sequence data of the genus Streptomyces have shown a far greater chemical diversity of metabolites than what have been discovered under typical laboratory fermentation conditions. In our previous natural product discovery efforts on Streptomyces sp. MA37, a bacterium isolated from the rhizosphere soil sample in Legon, Ghana, we discovered a handful of specialised metabolites from this talented strain. However, analysis of the draft genome of MA37 suggested that most of the encoded biosynthetic gene clusters (BGCs) remained cryptic or silent, and only a small fraction of BGCs for the production of specialised metabolites were expressed when cultured in our laboratory conditions. In order to induce the expression of the seemingly silent BGCs, we have carried out a co-culture experiment by growing the MA37 strain with the Gram-negative bacterium Pseudomonas sp. in a co-culture chamber that allows co-fermentation of two microorganisms with no direct contact but allows exchange of nutrients, metabolites, and other chemical cues. This co-culture approach led to the upregulation of several metabolites that were not previously observed in the monocultures of each strain. Moreover, the co-culture induced the expression of the cryptic indole alkaloid BGC in MA37 and led to the characterization of the known indolocarbazole alkaloid, BE-13793C 1. Neither bacterium produced compound 1 when cultured alone. The structure of 1 was elucidated by Nuclear Magnetic Resonance (NMR), mass spectrometry analyses and comparison of experimental with literature data. A putative biosynthetic pathway of 1 was proposed. Furthermore, BE-13793C 1 showed strong anti-proliferative activity against HT-29 (ATCC HTB-38) cells but no toxic effect to normal lung (ATCC CCL-171) cells. To the best of our knowledge, this is the first report for the activity of 1 against HT-29. No significant antimicrobial and anti-trypanosomal activities for 1 were observed. This research provides a solid foundation for the fact that a co-culture approach paves the way for increasing the chemical diversity of strain MA37. Further characterization of other upregulated metabolites in this strain is currently ongoing in our laboratory.

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Section: Proposed Biosynthetic Pathwaymentioning

confidence: 99%

A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite

et al. 2020

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“…In addition to being isolated from slime molds, bisindolylmaleimides have also now been found in bacterial culture broth extracts, suggesting the presence of bisindolylmaleimide biosynthetic gene clusters in bacterial genomes 8. Soil is thought to contain thousands of bacterial species per gram, with as much as 99 % of these bacteria being recalcitrant to culturing by standard methods 9.…”

Section: Methodsmentioning

confidence: 99%

Catalytic Effect of Cesium Cation Adduct Formation on the Decarboxylation of Carboxylate Ions in the Gas Phase

Mayeux

Massi

Gal

et al. 2013

Chemistry A European J

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The effect of Cs(+) ligation on the decarboxylation of malonic acids (unsubstituted and methyl-, dimethyl-, ethyl-, and phenyl-substituted) in their carboxylate form was studied in the gas phase using tandem mass spectrometry. The study is based on the comparison of the decarboxylation of the bare monoanion (hydrogen malonates) and of the cesium adduct of the cesium salt (Cs(+) [cesium hydrogen malonates]) under collisional activation. Energy-resolved dissociation curves of the negative and positive ions exhibit major differences. Decarboxylation of the cationic adducts of substituted malonic acid salts occurs at significantly lower collisional activation than for the corresponding bare hydrogen malonate anions. The conclusions from these experiments are supported by DFT calculations. The calculated activation parameters (enthalpy and Gibbs energy) confirm that the cesium cation coordination assists the decarboxylation of the carboxylate form.

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“…Further analysis confirmed not only the heterologous expression of both clusters, but also the elevated, in comparison with the native strains, level of production of chloramphenicol and congocidine. Two of these engineered S. coelicolor hosts, M1152 and M1154, have later been also found useful for heterologous expression of a wide spectrum of BGCs, such as the ones for indolocarbazole, aminocoumarines, liponucleoside and thiopeptides (Flinspach et al ., , ; Li et al ., ; Linares‐Otoya et al ., ). Additional engineering steps have been performed in order to make S. coelicolor M1152 to efficiently produce compounds biosynthesized by type III PKS (Thanapipatsiri et al ., ).…”

Section: Mining Of Bacterial Genomes For New Bioactive Natural Productsmentioning

confidence: 99%

Novel bioactive natural products from bacteria via bioprospecting, genome mining and metabolic engineering

Sekurova

Schneider

Zotchev

2019

Microbial Biotechnology

126

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Summary For over seven decades, bacteria served as a valuable source of bioactive natural products some of which were eventually developed into drugs to treat infections, cancer and immune system‐related diseases. Traditionally, novel compounds produced by bacteria were discovered via conventional bioprospecting based on isolation of potential producers and screening their extracts in a variety of bioassays. Over time, most of the natural products identifiable by this approach were discovered, and the pipeline for new drugs based on bacterially produced metabolites started to run dry. This mini‐review highlights recent developments in bacterial bioprospecting for novel compounds that are based on several out‐of‐the‐box approaches, including the following: (i) targeting bacterial species previously unknown to produce any bioactive natural products, (ii) exploring non‐traditional environmental niches and methods for isolation of bacteria and (iii) various types of ‘genome mining’ aimed at unravelling genetic potential of bacteria to produce secondary metabolites. All these approaches have already yielded a number of novel bioactive compounds and, if used wisely, will soon revitalize drug discovery pipeline based on bacterial natural products.

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Cloning, Characterization and Heterologous Expression of the Indolocarbazole Biosynthetic Gene Cluster from Marine-Derived Streptomyces sanyensis FMA

Cited by 33 publications

References 36 publications

A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite

A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite

Catalytic Effect of Cesium Cation Adduct Formation on the Decarboxylation of Carboxylate Ions in the Gas Phase

Novel bioactive natural products from bacteria via bioprospecting, genome mining and metabolic engineering

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