Versatile biocatalysis of fungal cytochrome P450 monooxygenases

Abstract

Cytochrome P450 (CYP) monooxygenases, the nature’s most versatile biological catalysts have unique ability to catalyse regio-, chemo-, and stereospecific oxidation of a wide range of substrates under mild reaction conditions, thereby addressing a significant challenge in chemocatalysis. Though CYP enzymes are ubiquitous in all biological kingdoms, the divergence of CYPs in fungal kingdom is manifold. The CYP enzymes play pivotal roles in various fungal metabolisms starting from housekeeping biochemical reactions, detoxification of chemicals, and adaptation to hostile surroundings. Considering the versatile catalytic potentials, fungal CYPs has gained wide range of attraction among researchers and various remarkable strategies have been accomplished to enhance their biocatalytic properties. Numerous fungal CYPs with multispecialty features have been identified and the number of characterized fungal CYPs is constantly increasing. Literature reveals ample reviews on mammalian, plant and bacterial CYPs, however, modest reports on fungal CYPs urges a comprehensive review highlighting their novel catalytic potentials and functional significances. In this review, we focus on the diversification and functional diversity of fungal CYPs and recapitulate their unique and versatile biocatalytic properties. As such, this review emphasizes the crucial issues of fungal CYP systems, and the factors influencing efficient biocatalysis.

Cloning and identification of a novel steroid 11α-hydroxylase gene from Absidia coerulea

“…Survey of the literature shows that diverse fungal species are capable of hydroxylating steroids [5]. Fungal steroid hydroxylases are members of the cytochrome P450 superfamily characterized by their high genetic diversity [17]. Because of the existence of dozens or even hundreds of cytochrome P450 isoforms in individual strains of many filamentous fungi [18] and low homology among cytochrome P450s catalyzing even the same type of oxidative reaction among closely related species [19,20], identification of steroid hydroxylase genes of interest in fungal strains is a significant challenge.…”

Biocatalyzed C−C Bond Formation for the Production of Alkaloids

“…The formation of C−C bonds plays a critical role in the connection of smaller substructures in order to synthesize complex organic structures and the carbon backbone of organic molecules ,,. Although challenging, the generation of multifunctional products is of enormous value .…”

“…Enzymatic strategies reduce the use of hazardous toxic chemical and intermediates, thereby providing a ‘greener’ alternative to the traditional chemical syntheses . Furthermore, a surge in demand for enantiopure pharmaceuticals, owing to the regulations imposed by various regulatory agencies, can be addressed using the exquisite mixture of enantio‐, regio‐ and, chemoselectivity displayed by enzymes ,. Enzymes can also be employed in multi‐enzymatic one‐pot cascades which can execute the synthesis of complex compounds from cheaper starting materials, most importantly, avoiding the purification of the intermediates …”

Heterologous coexpression of the benzoate‐para‐hydroxylase CYP53B1 with different cytochrome P450 reductases in various yeasts

“…Furthermore, current nucleic acid sequencing technologies are revealing vast numbers of P450s in plants (Mizutani, ) and even more so in fungi (Floudas et al ., ; Ichinose and Wariishi, ), representing immense reservoirs of potentially useful enzymes requiring functional characterization. Fungi in particular harbour a multitude of catalytically diverse P450s yet to be completely explored and harnessed (Durairaj et al ., ).…”

“…CYP53B1, a benzoate-para-hydroxylase (BpH) from Rhodotorula minuta (recently reclassified as Cytobasidium minutum), was chosen as an exemplary fungal P450, as CYP53 family members have been observed across all subclasses of basidiomycetous fungi, as well in the Pezizomycotina subclass of Ascomycetes (Jawallapersand et al, 2014). The hydroxylation of benzoic acid (BA) and its derivatives is a critical step in degradation of structural and protective compounds of plants, and as such these enzymes have been linked to persistence and pathogenesis of fungi to plants (Jawallapersand et al, 2014;Durairaj et al, 2016). In fact, this is one of three P450 families highly conserved among biotrophic plant pathogenic fungi, with the other two families involved in membrane ergosterol biosynthesis, highlighting their importance (Qhanya et al, 2015).…”