CYP105-diverse structures, functions and roles in an intriguing family of enzymes inStreptomyces

Abstract

The cytochromes P450 (CYP or P450) are a large superfamily of haem-containing enzymes found in all domains of life. They catalyse a variety of complex reactions, predominantly mixed-function oxidations, often displaying highly regio- and/or stereospecific chemistry. In streptomycetes, they are predominantly associated with secondary metabolite biosynthetic pathways or with xenobiotic catabolism. Homologues of one family, CYP105, have been found in all Streptomyces species thus far sequenced. This review looks at the diverse biological functions of CYP105s and the biosynthetic/catabolic pathways they are associated with. Examples are presented showing a range of biotransformative abilities and different contexts. As biocatalysts capable of some remarkable chemistry, CYP105s have great biotechnological potential and merit detailed study. Recent developments in biotechnological applications which utilize CYP105s are described, alongside a brief overview of the benefits and drawbacks of using P450s in commercial applications. The role of CYP105s in vivo is in many cases undefined and provides a rich source for further investigation into the functions these enzymes fulfil and the metabolic pathways they participate in, in the natural environment.

Phylogenomics reveals dynamic evolution of fungal nitric oxide reductases and their relationship to secondary metabolism

“…p450nor is actinobacterial in origin, yet Actinobacteria are not considered canonical denitrifiers and evidence for their role in denitrification was lacking when p450nor was initially identified (29, 45). Subsequent investigations did not posit a role for p450nor in SM despite the affiliation of p450nor and CYP105 P450s with documented roles in SM (34, 46). To assess genomic evidence linking p450nor to SM, we queried genes encoded within genomic regions approximately 50 kb on either side of p450nor for functions related to SM.…”

“…The SM hypothesis has traction considering that P450nor is derived from CYP105 P450s (Fig. 2), all of which share a functional role in SM (34, 46, 60). Thus, the adaptation of P450nor to a novel niche in NO reduction and denitrification is unlikely.…”

Metabolic responses of Rhodococcus erythropolis PR4 grown on diesel oil and various hydrocarbons

“…Our study revealed the potential role of other types of cytochrome P450 in the biodegradation of hydrocarbons, such as CYP51B, CYP105, CYP123, CYP125 and CYP136. CYP51B was described as a sterol-demethylase (Bellamine et al 1999), CYP105 seems to have diverse functions in catabolism of xenobiotics (Moody and Loveridge 2014. ), while CYP125 was found to catalyze the terminal hydroxylation of steroids (Capyk et al 2009).…”

Unrivalled diversity: the many roles and reactions of bacterial cytochromes P450 in secondary metabolism

“…4 Whilst relatively successful in higher eukaryotes, this approach has limited utility in bacterial systems, where substrate selectivity and catalytic function can vary widely within P450 families -classic examples of P450 families that encompass members displaying highly diverse functions include the CYP105, CYP107 and CYP109 families. 2,3,5,6 Thus, care must be taken in assigning P450 functions in bacteria based purely on sequence conservation data, unless the level of conservation is very high (>55-65%).…”