Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi

Tran, Phuong; Yen, Ming‐Ren; Chiang, Chen‐Yu; Lin, Hsiao‐Ching; Chen, Pao‐Yang

doi:10.1007/s00253-019-09708-z

Cited by 86 publications

(72 citation statements)

References 105 publications

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“…Analysis of association of P450s with BGCs revealed that specific P450 orthologues are involved in the production of the same secondary metabolite (Table 4), indicating horizontal gene transfer of these BGCs among Bacillus species, a well-known phenomenon of gene-cluster transfer between bacterial species 33,64,65 . Prominent observations include CYP107K P450s' involvement in biosynthesis of bacillaene, CYP113L1 P450s' involvement in the biosynthesis of difficidin and CYP107H4 P450s' involvement in the biosynthesis of fengycin (Table 4).…”

Section: Most Firmicutes Species P450s Are Orphans Of Unknown Functiomentioning

confidence: 99%

Impact of lifestyle on cytochrome P450 monooxygenase repertoire is clearly evident in the bacterial phylum Firmicutes

Padayachee

Nzuza

Chen

et al. 2020

Sci Rep

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Cytochrome P450 monooxygenases (CYPs/P450s), heme thiolate proteins, are well known for their role in organisms' primary and secondary metabolism. Research on eukaryotes such as animals, plants, oomycetes and fungi has shown that P450s profiles in these organisms are affected by their lifestyle. However, the impact of lifestyle on P450 profiling in bacteria is scarcely reported. This study is such an example where the impact of lifestyle seems to profoundly affect the P450 profiles in the bacterial species belonging to the phylum Firmicutes. Genome-wide analysis of P450s in 972 Firmicutes species belonging to 158 genera revealed that only 229 species belonging to 37 genera have P450s; 38% of Bacilli species, followed by 14% of Clostridia and 2.7% of other Firmicutes species, have P450s. The pathogenic or commensal lifestyle influences P450 content to such an extent that species belonging to the genera Streptococcus, Listeria, Staphylococcus, Lactobacillus, Lactococcus and Leuconostoc do not have P450s, with the exception of a handful of Staphylococcus species that have a single P450. Only 18% of P450s are found to be involved in secondary metabolism and 89 P450s that function in the synthesis of specific secondary metabolites are predicted. This study is the first report on comprehensive analysis of P450s in Firmicutes. Among the bacteria that inhabit the human gut, species belonging to the bacterial phylum Firmicutes and Bacteroides are dominant 1-3. Firmicutes species are gram-positive microorganisms with rod or sphere shapes and reproduce via binary fission. This phylum contains bacteria possessing diverse characteristics that are adapted to diverse ecological niches. Some members are saprophytes that live in soil and aquatic environments, performing mainly decomposition and recycling of organic matter, some members are commensals of humans and some members are pathogens of animals, including humans, and plants 4. Some members have been subjected to thorough investigation to gain understanding of endospore formation and survival 5 and the biotechnological potential of these organisms has been explored for the production of dairy products 6 , enzymes 7 and antibiotics 8. The Firmicutes phylum is further divided into seven subphyla, namely Bacilli, Clostridia, Erysipelotrichia, Limnochordia, Negativicutes, Thermolithobacteria, and Tissierellia 4. Species belonging to the subphyla Bacilli are well known for the production of secondary metabolites valuable to humans, organic compounds that have medicinal properties (Table 1). Clostridia consist of species that produce short chain fatty acids in the human gut, such as butyrate, which is essential fuel for colonocytes (enterocytes referred to as colonocytes in the colon) 9 and also species causing botulism, tetanus, gas gangrene, food poisoning, pseudomembranous colitis, and antibioticassociated diarrhea in humans 10,11. Quite a number of studies have explored the relation between the changes in the percentage of Firmicutes species in the human gut and human conditi...

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Section: Most Firmicutes Species P450s Are Orphans Of Unknown Functiomentioning

confidence: 99%

Impact of lifestyle on cytochrome P450 monooxygenase repertoire is clearly evident in the bacterial phylum Firmicutes

Padayachee

Nzuza

Chen

et al. 2020

Sci Rep

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“…[17] Direct digital extraction of chemical shifts from the raw data [18] will push the protocol closer to native computational interrogation. This in turn will expedite the growth of the database,which we anticipate will eventually be able to assign the structural features of each carbon and proton within ag iven molecule.W hile structural assignment is ak ey facet of the drug discovery process,t he ability to search through molecular data one atom at at ime offers an ew perspective that can enable this system to operate through aconventional online portal, one that ideally will be united with biosynthetic genome mining tools [19] such as antiSMASH, [20] as well as proteomic [21] and transcriptomic [22] data. Ultimately,i tw ill be interesting to understand the correlation between structural novelty and its role in inducing novel biological activity,p erhaps done best one atom at atime.…”

mentioning

confidence: 99%

Searching for Small Molecules with an Atomic Sort

et al. 2019

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The discovery of biologically active small molecules requires sifting through large amounts of data to identify unique or unusual arrangements of atoms. Here, we develop, test and evaluate an atom‐based sort to identify novel features of secondary metabolites and demonstrate its use to evaluate novelty in marine microbial and sponge extracts. This study outlines an important ongoing advance towards the translation of autonomous systems to identify, and ultimately elucidate, atomic novelty within a complex mixture of small molecules.

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“…It has been reported that most BGCs remain silent and cannot be fully expressed under standard laboratory conditions. These silent BGCs are potentially significant in the discovery of novel SMs [10][11][12]43].…”

Section: Genomic For Screening and Enhancement Of Sms 21 Gene Editinmentioning

confidence: 99%

Enhancement and Identification of Microbial Secondary Metabolites

Shuikan¹,

Hozzein²,

Alzharani³

et al. 2021

Extremophilic Microbes and Metabolites - Diversity, Bioprospecting and Biotechnological Applications

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Screening for microbial secondary metabolites (SMs) has attracted the attention of the scientific community since 1940s. In fact, since the discovery of penicillin, intensive researches have been conducted worldwide in order to detect and identify novel microbial secondary metabolites. As a result, the discovery of novel SMs has been decreased significantly by using traditional experiments. Therefore, searching for new techniques to discover novel SMs was one of the most priority objectives. However, the development and advances of omics-based techniques such as metabolomics and genomics have revealed the potential of discovering novel SMs which were coded in the microorganisms' DNA but not expressed in the lab media or might be produced in undetectable amount by detecting the biosynthesis gene clusters (BGCs) that are associated with the biosynthesis of secondary metabolites. Nowadays, the development and integration of gene editing tools such as CRISPR-Cas9 in metabolomics provide a successful platform for the identification and detection of known and novel SMs and also to increase the production of SMs.

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Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi

Cited by 86 publications

References 105 publications

Impact of lifestyle on cytochrome P450 monooxygenase repertoire is clearly evident in the bacterial phylum Firmicutes

Impact of lifestyle on cytochrome P450 monooxygenase repertoire is clearly evident in the bacterial phylum Firmicutes

Searching for Small Molecules with an Atomic Sort

Enhancement and Identification of Microbial Secondary Metabolites

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