Microbial Cytochromes P450

McLean, Kirsty J.; Leys, D.; Munro, Andrew W.

doi:10.1007/978-3-319-12108-6_6

Cited by 25 publications

(27 citation statements)

References 847 publications

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“…Itraconazole inhibits certain cytochrome P450 enzymes (Schuster, ), which are sometimes expressed by prokaryotes. Little information is available on which bacterial genera express them; but investigations of some Pseudomonas , Bacillus , Acinetobacter , and Sphingomonas species have failed to detect the expression of these enzymes (McLean, Leys & Munro, ). We did not investigate the role of the adaptive immune system in these frogs, which could also provide protection from chytridiomycosis.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous bacteria, but not peptides, are associated with chytridiomycosis resistance in Peruvian marsupial frogs

Burkart

Flechas

Vredenburg

et al. 2017

Animal Conservation

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Amphibians are a highly threatened vertebrate group, and populations of these animals have declined drastically. An important global threat to amphibians is the pathogenic fungus Batrachochytrium dendrobatidis (Bd), which causes the disease chytridiomycosis. However, not all species develop chytridiomycosis when exposed to Bd. We compared susceptibility to disease in two species of marsupial frogs and found that Gastrotheca nebulanastes is susceptible, whereas its congeneric G. excubitor is resistant. Since Bd is a skin pathogen, it is possible that cutaneous defenses like symbiotic bacteria and antimicrobial peptides protect the resistant species. We tested this hypothesis by comparing the anti-Bd abilities of cutaneous defenses between the two Gastrotheca species. Cultivable bacteria and peptides were isolated from the skin and tested for their abilities to inhibit Bd with in vitro co-culture assays. Twenty-six bacteria were identified by sequencing their 16S rRNA gene and 19 peptides were profiled by MALDI TOF mass spectrometry. We found that bacteria, but not peptides, differed between the two species in their ability to inhibit Bd growth. The resistant G. excubitor harbored more isolates of cultivable anti-Bd bacteria both in number and proportion (6/15 vs. 1/11). Also, the one anti-Bd isolate from G. nebulanastes demonstrated the weakest ability to inhibit Bd growth. Our results highlight the importance of anti-Bd skin bacteria in providing frog species with protection from Bd and can inform mitigation strategies for other wildlife diseases.

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Section: Discussionmentioning

confidence: 99%

Cutaneous bacteria, but not peptides, are associated with chytridiomycosis resistance in Peruvian marsupial frogs

Burkart

Flechas

Vredenburg

et al. 2017

Animal Conservation

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“…This becomes anecdotally apparent when one considers two facts: (i) the sheer numbers of P450s found in the most prevalent producers of natural products, including plants, fungi, and the actinomycetes (see online databases http://drnelson.uthsc.edu/cytochromeP450.html and http://p450.riceblast.snu.ac.kr), 4,5,31,52,53 and (ii) the frequency of P450-encoding genes found within known and putative secondary metabolite gene clusters. The tremendous diversity in natural product structures requires diversity in the enzymes that act on them, and P450s are no exception.…”

Section: Functionmentioning

confidence: 99%

“…The largest supercluster is composed of both the CYP105 and CYP107 families, the two largest CYP families in bacteria. 4 Smaller clusters and singletons, P450s that are not present in many different species, likely have evolved specific functions for less common biosynthetic pathways or substrates. (iii) At this similarity level, there are no overall tendencies of P450s of similar function or preferred substrate to cluster together.…”

Section: Sequencementioning

confidence: 99%

Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

et al. 2017

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Cytochrome P450 enzymes (P450s) are some of the most exquisite and versatile biocatalysts found in nature. In addition to their well-known roles in steroid biosynthesis and drug metabolism in humans, P450s are key players in natural product biosynthetic pathways. Natural products, the most chemically and structurally diverse small molecules known, require an extensive collection of P450s to accept and functionalize their unique scaffolds. In this review, we survey the current catalytic landscape of P450s within the Streptomyces genus, one of the most prolific producers of natural products, and comprehensively summarize the functionally characterized P450s from Streptomyces. A sequence similarity network of >8500 P450s revealed insights into the sequence–function relationships of these oxygen-dependent metalloenzymes. Although only ~2.4% and <0.4% of streptomycete P450s have been functionally and structurally characterized, respectively, the study of streptomycete P450s involved in the biosynthesis of natural products has revealed their diverse roles in nature, expanded their catalytic repertoire, created structural and mechanistic paradigms, and exposed their potential for biomedical and biotechnological applications. Continued study of these remarkable enzymes will undoubtedly expose their true complement of chemical and biological capabilities.

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“…Since their identification five decades ago, quite a large number of P450s have been identified in species across biological kingdoms, especially due to the current genome sequencing rush 2 . Studies on P450 enzymes have been reported from animals owing to their role in drug metabolism (particularly from mammals) 3 or analysis of diversity 1 4 ; from fungi owing to their role as drug targets 5 6 and for evolutionary analysis 7 8 9 ; from bacteria owing to P450 structure-functional analysis 10 and generation of products valuable to humans 11 ; and from plants owing to their roles in key cellular processes and defense mechanisms 12 13 14 . Irrespective of their origins, P450s from all organisms have been exploited for their biotechnological potential 15 .…”

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confidence: 99%

Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s

Parvez

Qhanya

Mthakathi

et al. 2016

Sci Rep

110

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Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria −42; fungi −19; plant −28; animal −22; plant and animal −1 and common P450 family −1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study’s results offer new understanding of the dynamic structural nature of P450s.

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Microbial Cytochromes P450

Cited by 25 publications

References 847 publications

Cutaneous bacteria, but not peptides, are associated with chytridiomycosis resistance in Peruvian marsupial frogs

Cutaneous bacteria, but not peptides, are associated with chytridiomycosis resistance in Peruvian marsupial frogs

Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function

Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s

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