More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium

Mnguni, Fanele Cabangile; Padayachee, Tiara; Chen, Wanping; Gront, Dominik; Yu, Jae‐Hyuk; Nelson, David R.; Syed, Khajamohiddin

doi:10.3390/ijms21134814

Cited by 22 publications

(54 citation statements)

References 106 publications

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“…However, P450s from Firmicutes species are only second to Streptomyces species P450s (23%) in terms of their involvement in secondary metabolism (Table 2 ). These results strongly support the recent observation that more P450s are involved in secondary metabolism in Streptomyces species compared to other bacterial species 46 and it is no surprise that two thirds of all known antibiotics in the world come from these species 54 .…”

Section: Resultssupporting

confidence: 89%

“…of P450s 1 27 30 3 No. of P450s part of BGCs 126 1231 204 27 Percentage of P450s part of BGCs 18 23 11 8 Reference(s) This work 45 , 46 45 , 47 49 BGC , biosynthetic gene cluster. …”

Section: Resultsmentioning

confidence: 99%

“…Cyanobacterial species also had no P450 family conserved, but P450 families CYP110 and CYP120 were found to be a co-presence in most of these species 49 . the large CYP107 family was found to be conserved in Streptomyces species 46 and quite a number of P450 families were found to be conserved in mycobacterial species 47 .

Figure 3 Analysis of presence of P450 family (red) or its absence (green) in 229 Firmicutes species.…”

Section: Resultsmentioning

confidence: 99%

“…An interesting comparison can be drawn between the role of secondary metabolites produced by Firmicutes where P450s are involved (Table 4 ) and the role of secondary metabolites produced by Streptomyces species 45 , 46 . In both cases, these secondary metabolites seem to be helping organisms gain the upper hand in their ecological niches, as the secondary metabolites produced by these organisms have anti-bacterial, anti-fungal and anti-viral properties, suggesting that these compounds help both the Firmicutes 8 and the Streptomyces 45 , 46 species to thrive in their ecological niches by eliminating other organisms. The structure and biological functions of bacillaene, difficidin, fengycin, lichenysin, macrolactin, rhizocticin and surfactin produced by Firmicutes were recently reviewed 8 .…”

Section: Resultsmentioning

confidence: 99%

“…Studies on the role of P450s in organism’s adaptations or changes in P450 profiles according to an organism’s life have been conducted on eukaryotic organisms such as fungi 34 – 41 , oomycetes 42 , plants 43 , and animals 44 . However, this phenomenon is scarcely reported in prokaryotes; currently data are available only for bacterial species belonging to the genera Streptomyces 45 , 46 , Mycobacterium 47 , 48 and the phylum Cyanobacteria 49 , suggesting that more research is needed to unravel P450s’ role in other bacterial species. The presence of species with diverse characteristics that are adapted to diverse ecological niches, such as in Firmicutes, will enhance understanding of the role of P450s in bacterial species, especially with respect to their role in those organism’s adaptations.…”

Section: Introductionmentioning

confidence: 99%

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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: Resultssupporting

confidence: 89%

“…of P450s 1 27 30 3 No. of P450s part of BGCs 126 1231 204 27 Percentage of P450s part of BGCs 18 23 11 8 Reference(s) This work 45 , 46 45 , 47 49 BGC , biosynthetic gene cluster. …”

Section: Resultsmentioning

confidence: 99%

Figure 3 Analysis of presence of P450 family (red) or its absence (green) in 229 Firmicutes species.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Padayachee

Nzuza

Chen

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

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Microbial P450 repertoire (P450ome) and its application feasibility in pharmaceutical industry, chemical industry, and environmental protection

Wang,

Pan,

Wang

et al. 2023

Biotech & Bioengineering

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Cytochrome P450s (CYPs) are heme‐thiolated enzymes that catalyze the oxidation of C‐H bonds in a regio‐ and stereo‐selective manner. CYPs are widely present in the biological world. With the completion of more biological genome sequencing, the number and types of P450 enzymes have increased rapidly. P450 in microorganisms is easy to clone and express, rich in catalytic types, and strong in substrate adaptability, which has good application potential. Although the number of P450 enzymes found in microorganisms is huge, the function of most of the microorganism P450s has not been studied, and it contains a large number of excellent biocatalysts to be developed. This review is based on the P450 groups in microorganisms. First, it reviews the distribution of P450 groups in different microbial species, and then studies the application of microbial P450 enzymes in the pharmaceutical industry, chemical industry and environmental pollutant treatment in recent years. And focused on the application fields of P450 enzymes of different families to guide the selection of suitable P450s from the huge P450 library. In view of the current shortcomings of microbial P450 in the application process, the final solution is the most likely to assist the application of P450 enzymes in large‐scale, that is, whole cell transformation combined with engineering, fusion P450 combined with immobilization technology.

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The 16α‐Hydroxylation of Progesterone by Cytochrome P450 107X1 from Streptomyces avermitilis

Lin

Gao

et al. 2022

Chemistry & Biodiversity

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Cytochrome P450 enzymes (CYPs or P450s) are ubiquitous heme‐dependent enzymes that catalyze the monooxygenation of non‐activated C−H bonds to modify the structure of the substrate. In this study, we heterologously expressed CYP107X1 from Streptomyces avermitilis and conducted in vitro substrate screening using the alternative redox partners putidaredoxin and putidaredoxin reductase. CYP107X1 catalyzed the 16α‐hydroxylation of progesterone with regio‐ and stereoselectivity. The spectroscopic analyses showed that CYP107X1 bound progesterone with a relatively high Kd value of 65.3±38.9 μM. The Km and kcat values for progesterone were estimated to be 47.7±12.0 μM and 0.30 min−1, respectively. Furthermore, a crystal structure was obtained of CYP107X1 bound with glycerol from the buffer solution. Interestingly, a conserved threonine was replaced with asparagine in CYP107X1, indicating that it may adopt an unnatural proton transfer process and play a crucial role in its catalytic activity.

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More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium

Cited by 22 publications

References 106 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

Microbial P450 repertoire (P450ome) and its application feasibility in pharmaceutical industry, chemical industry, and environmental protection

The 16α‐Hydroxylation of Progesterone by Cytochrome P450 107X1 from Streptomyces avermitilis

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