Dataset Information

Similarities, variations, and evolution of cytochrome P450s in Streptomyces versus Mycobacterium.

ABSTRACT: Cytochrome P450 monooxygenases (P450s) found in all domains of life are known for their catalytic versatility and stereo- and regio-specific activity. While the impact of lifestyle on P450 evolution was reported in many eukaryotes, this remains to be addressed in bacteria. In this report, Streptomyces and Mycobacterium, belonging to the phylum Actinobacteria, were studied owing to their contrasting lifestyles and impacts on human. Analyses of all P450s and those predicted to be associated with secondary metabolism have revealed that different lifestyles have affected the evolution of P450s in these bacterial genera. We have found that while species in both genera have essentially the same number of P450s in the genome, Streptomyces P450s are much more diverse than those of Mycobacterium. Moreover, despite both belonging to Actinobacteria, only 21 P450 families were common, and 123 and 56 families were found to be unique to Streptomyces and Mycobacterium, respectively. The presence of a large and diverse number of P450s in Streptomyces secondary metabolism contributes to antibiotic diversity, helping to secure the niche. Conversely, based on the currently available functional data, types of secondary metabolic pathways and associated P450s, mycobacterial P450s seem to play a role in utilization or synthesis of lipids.

SUBMITTER: Senate LM

PROVIDER: S-EPMC6408508 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Similarities, variations, and evolution of cytochrome P450s in Streptomyces versus Mycobacterium.

Senate Louisa Moshoeshoe LM Tjatji Martin Phalane MP Pillay Kayla K Chen Wanping W Zondo Ntokozo Minenhle NM Syed Puleng Rosinah PR Mnguni Fanele Cabangile FC Chiliza Zinhle Edith ZE Bamal Hans Denis HD Karpoormath Rajshekhar R Khoza Thandeka T Mashele Samson Sitheni SS Blackburn Jonathan Michael JM Yu Jae-Hyuk JH Nelson David R DR Syed Khajamohiddin K

Scientific reports 20190308 1

Cytochrome P450 monooxygenases (P450s) found in all domains of life are known for their catalytic versatility and stereo- and regio-specific activity. While the impact of lifestyle on P450 evolution was reported in many eukaryotes, this remains to be addressed in bacteria. In this report, Streptomyces and Mycobacterium, belonging to the phylum Actinobacteria, were studied owing to their contrasting lifestyles and impacts on human. Analyses of all P450s and those predicted to be associated with s ...[more]

PMID: 30850694

Similar Datasets

Project description:The superfamily of cytochrome P450s forms a large class of heme monooxygenases with more than 13,000 enzymes represented in organisms from all biological kingdoms. Despite impressive variability in sizes, sequences, location, and function, all cytochrome P450s from various organisms have very similar tertiary structures within the same fold. Here we show that systematic comparison of all available X-ray structures of cytochrome P450s reveals the presence of two distinct structural classes of cytochrome P450s. For all membrane bound enzymes, except the CYP51 family, the beta-domain and the A-propionate heme side chain are shifted towards the proximal side of the heme plane, which may result in an increase of the volume of the substrate binding pocket and an opening of a potential channel for the substrate access and/or product escape directly into the membrane. This structural feature is also observed in several soluble cytochrome P450s, such as CYP108, CYP151, and CYP158A2, which catalyze transformations of bulky substrates. Alternatively, both beta-domains and the A-propionate side chains in the soluble isozymes extend towards the distal site of the heme. This difference between the structures of soluble and membrane bound cytochrome P450s can be rationalized through the presence of several amino acid inserts in the latter class which are involved in direct interactions with the membrane, namely the F'- and G'-helices. Molecular dynamics using the most abundant human cytochrome P450, CYP3A4, incorporated into a model POPC bilayer reveals the facile conservation of a substrate access channel, directed into the membrane between the B-C loop and the beta domain, and the closure of the peripheral substrate access channel directed through the B-C loop. This is in contrast to the case when the same simulation is run in buffer, where no such channel closing occurs. Taken together, these results reveal a key structural difference between membrane bound and soluble cytochrome P450s with important functional implications induced by the lipid bilayer.

Project description:BackgroundHoney bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored.Methodology/principal findingsWe used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau-fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey.Conclusions/significanceThese results suggest that regulation of honey bee P450s is tuned to chemicals occurring naturally in the hive environment and that, in terms of toxicological capacity, a diet of sugar is not equivalent to a diet of honey.

Dataset Information

Similarities, variations, and evolution of cytochrome P450s in Streptomyces versus Mycobacterium.

Publications

Similarities, variations, and evolution of cytochrome P450s in Streptomyces versus Mycobacterium.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets