A promiscuous cytochrome P450 aromatic O-demethylase for lignin bioconversion

Mallinson, S.J.B.; Machovina, Melodie M.; Silveira, Rodrigo L.; Garcia‐Borràs, Marc; Gallup, Nathan M.; Johnson, Christopher W.; Allen, Mark D.; Skaf, Munir S.; Crowley, Michael F.; Neidle, Ellen L.; Houk, K. N.; Beckham, Gregg T.; DuBois, Jennifer L.; McGeehan, J.E.

doi:10.1038/s41467-018-04878-2

Cited by 160 publications

(204 citation statements)

References 74 publications

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“…However, TP 203 and PA could also be produced from TPs 217 and 203, respectively, by cytochrome P450-dependent O-demethylation reactions (Girvan and Munro, 2016). O-demethylation reactions are well-known from fungi, where cytochrome P450 lanosterol 14α-demethylase is a prominent target for antifungal agents (Durairaj et al, 2016;Wang et al, 2019), and also from bacteria (Mallinson et al, 2018). The successive demethylation of TP 217 (dimethyl phthalate ester) via TP 203 (monomethyl phthalate ester) to PA was proposed for complex microbial communities of soil (Cartwright et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Biotransformation of Phthalate Plasticizers and Bisphenol A by Marine-Derived, Freshwater, and Terrestrial Fungi

et al. 2020

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Phthalate esters (PEs, Phthalates) are environmentally ubiquitous as a result of their extensive use as plasticizers and additives in diverse consumer products. Considerable concern relates to their reported xenoestrogenicity and consequently, microbial-based attenuation of environmental PE concentrations is of interest to combat harmful downstream effects. Fungal PE catabolism has received less attention than that by bacteria, and particularly fungi dwelling within aquatic environments remain largely overlooked in this respect. We have compared the biocatalytic and biosorptive removal rates of din -butyl phthalate (DBP) and diethyl phthalate (DEP), chosen to represent two environmentally prominent PEs of differing structure and hydrophobicity, by marine-, freshwater-, and terrestrial-derived fungal strains. Bisphenol A, both an extensively used plastic additive and prominent environmental xenoestrogen, was included as a reference compound due to its well-documented fungal degradation. Partial pathways of DBP metabolization by the ecophysiologically diverse asco-and basidiomycete strains tested were proposed with the help of UPLC-QTOF-MS analysis. Species specific biochemical reaction steps contributing to DBP metabolism were also observed. The involved reactions include initial cytochrome P450-dependent monohydroxylations of DBP with subsequent further oxidation of related metabolites, de-esterification via either hydrolytic cleavage or cytochrome P450-dependent oxidative O-dealkylation, transesterification, and demethylation steps-finally yielding phthalic acid as a central intermediate in all pathways. Due to the involvement of ecophysiologically and phylogenetically diverse filamentous and yeast-like fungi native to marine, freshwater, and terrestrial habitats the results of this study outline an environmentally ubiquitous pathway for the biocatalytic breakdown of plastic additives. Beyond previous research into fungal PE metabolism which emphasizes hydrolytic de-esterification as the primary catabolic step, a prominent role of cytochrome P450 monooxygenase-catalyzed reactions is established.

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Section: Discussionmentioning

confidence: 99%

Biotransformation of Phthalate Plasticizers and Bisphenol A by Marine-Derived, Freshwater, and Terrestrial Fungi

et al. 2020

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“…Despite many known variations in these components (39), a reductase with the domain structure of GcoB has not previously been reported to interact with a cytochrome P450 enzyme. Characterization of GcoAB, including its atomic-level structure and substrate specificity, are reported in a companion paper (40).…”

Section: Discussionmentioning

confidence: 99%

Accelerating pathway evolution by increasing the gene dosage of chromosomal segments

Tumen-Velasquez

Johnson

Ahmed

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Experimental evolution is a critical tool in many disciplines, including metabolic engineering and synthetic biology. However, current methods rely on the chance occurrence of a key step that can dramatically accelerate evolution in natural systems, namely increased gene dosage. Our studies sought to induce the targeted amplification of chromosomal segments to facilitate rapid evolution. Since increased gene dosage confers novel phenotypes and genetic redundancy, we developed a method, Evolution by Amplification and Synthetic Biology (EASy), to create tandem arrays of chromosomal regions. In Acinetobacter baylyi, EASy was demonstrated on an important bioenergy problem, the catabolism of lignin-derived aromatic compounds. The initial focus on guaiacol (2-methoxyphenol), a common lignin degradation product, led to the discovery of Amycolatopsis genes (gcoAB) encoding a cytochrome P450 enzyme that converts guaiacol to catechol. However, chromosomal integration of gcoAB in Pseudomonas putida or A. baylyi did not enable guaiacol to be used as the sole carbon source despite catechol being a growth substrate. In ∼1,000 generations, EASy yielded alleles that in single chromosomal copy confer growth on guaiacol. Different variants emerged, including fusions between GcoA and CatA (catechol 1,2-dioxygenase). This study illustrates the power of harnessing chromosomal gene amplification to accelerate the evolution of desirable traits.

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“…In addition, a vanillin self-inducible promoter ADH7 from S. cerevisiae was introduced in E. coli to eliminate the cost of an external inducer [45]. Besides PCA decarboxylation, catechol can also be produced from guaiacol, a product of lignin depolymerization, via expressing a cytochrome P450 aromatic O-demethylase from the family CYP255A (GcoA) and a three-domain reductase (GcoB) in P. putida [46]. Syringic acid can be produced from syringaldehyde, one of the lignin-derived aromatic molecules, by heterologous expression of desV or ligV in E. coli [47].…”

Section: Production Of Aromatic Chemicalsmentioning

confidence: 99%

Lignin valorization meets synthetic biology

Zhang

Zhao

Chang

et al. 2019

Engineering in Life Sciences

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Lignin, an abundant renewable resource in nature, is a highly heterogeneous biopolymer consisting of phenylpropanoid units. It is essential for sustainable utilization of biomass to convert lignin to value‐added products. However, there are technical obstacles for lignin valorization due to intrinsic heterogeneity. The emerging of synthetic biology technologies brings new opportunities for lignin breakdown and utilization. In this review, we discussed the applications of synthetic biology on lignin conversion, especially the production of value‐added products, such as aromatic chemicals, ring‐cleaved chemicals from lignin‐derived aromatics and bio‐active substances. Synthetic biology will offer new potential strategies for lignin valorization by optimizing lignin degradation enzymes, building novel artificial converting pathways, and improving the chassis of model microorganisms.

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A promiscuous cytochrome P450 aromatic O-demethylase for lignin bioconversion

Cited by 160 publications

References 74 publications

Biotransformation of Phthalate Plasticizers and Bisphenol A by Marine-Derived, Freshwater, and Terrestrial Fungi

Biotransformation of Phthalate Plasticizers and Bisphenol A by Marine-Derived, Freshwater, and Terrestrial Fungi

Accelerating pathway evolution by increasing the gene dosage of chromosomal segments

Lignin valorization meets synthetic biology

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