Zinhle Chiliza - Academia.edu (original) (raw)

Papers by Zinhle Chiliza

Biophysical Reviews, Sep 3, 2020

Cytochrome P450 monooxygenases (CYPs/P450s) are heme-thiolate proteins that are ubiquitously pres... more Cytochrome P450 monooxygenases (CYPs/P450s) are heme-thiolate proteins that are ubiquitously present in organisms, including non-living entities such as viruses. With the exception of self-sufficient P450s, all other P450 enzymes need electrons to perform their enzymatic activity and these electrons are supplied by P450 redox proteins. Different types of P450 redox proteins can be found in organisms and are classified into different classes. Bacterial P450s (class I) receive electrons from ferredoxins which are iron-sulfur cluster proteins. The presence of more than one copy and different types of ferredoxins within a bacterial species poses fundamental questions about the selectivity of P450s and ferredoxins in relation to each other. Apart from transferring electrons, ferredoxins have also been found to modulate P450 functions. Achieving an understanding of the interaction between ferredoxins and P450s is required to harness their biotechnological potential for designing a universal electron transfer protein. A brief overview of factors playing a role in ferredoxin and P450 interactions is presented in this review article.

International Journal of Molecular Sciences

Cytochrome P450 monooxygenases (CYPs/P450s) are well known for their role in organisms’ primary a... more Cytochrome P450 monooxygenases (CYPs/P450s) are well known for their role in organisms’ primary and secondary metabolism. Among 20 P450s of the tuberculosis-causing Mycobacterium tuberculosis H37Rv, CYP128A1 is particularly important owing to its involvement in synthesizing electron transport molecules such as menaquinone-9 (MK9). This study employs different in silico approaches to understand CYP128 P450 family’s distribution and structural aspects. Genome data-mining of 4250 mycobacterial species has revealed the presence of 2674 CYP128 P450s in 2646 mycobacterial species belonging to six different categories. Contrast features were observed in the CYP128 gene distribution, subfamily patterns, and characteristics of the secondary metabolite biosynthetic gene cluster (BGCs) between M. tuberculosis complex (MTBC) and other mycobacterial category species. In all MTBC species (except one) CYP128 P450s belong to subfamily A, whereas subfamily B is predominant in another four mycobacter...

Scientific Reports

Cytochrome P450 monooxygenases (P450s) found in all domains of life are known for their catalytic... more 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. Cytochrome P450 monooxygenases (P450s/CYPs) are ubiquitously distributed in all domains of life, and even found in some non-living entities such as viruses 1,2. P450s are catalytically versatile and cause stereo-and regio-specific enzymatic reactions 3,4. Because of this unique nature, P450s have been in focus for more than five decades 5. Whole genome sequencing of various organisms belonging to different biological domains and kingdoms have resulted in identification of more than 300,000 P450s 2. Analyses of P450 evolutionary patterns with respect to species and their ecological niches is gaining a great momentum. This type of study has been reported