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.

Keywords: Biocatalysis; Cytochrome P450; Cytochrome P450 reductase; Fungi; Monooxygenase reaction.

Fig. 1

CYP catalytic cycle and schematic representation of the interaction of CYP-CPR for class II CYP system

Fig. 2

Representative scheme of functional diversification and classification of fungal CYP systems. Categorization of the functional properties of Class II CYP systems based on the primary metabolism, secondary metabolism and xenobiotic detoxification was perceived from Ref. [16]

Fig. 3

Versatile monooxygenase reactions catalysed by fungal cytochrome P450 enzymes. a Selected examples of reaction products of fungal CYPs. b Selected examples of multifunctional reactions of fungal CYPs. The products were generated through multiple consecutive catalytic reaction mediated by a single CYP. Newly introduced hydroxyl groups and bonds are shown in red

Fig. 4

Catalytic potentials of fungal CYPs identified through functional screening. Representative examples of CYPs from P. chrsosporium, A. oryzae and P. placenta are presented in black, blue and red, respectively. The CYP names are denoted excluding “CYP”. For example, CYP512C1 is abbreviated as 512C1