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[Antioxidants]Molecular Properties of β-Carotene Oxygenases and Their Potential in Industrial Production of Vitamin A and Its Derivatives, 2022, 11(6), 1180;
Kyung-Chul Shin, Soo-Jin Yeom
Figure 4. Strategies for the improvement of retinal production via protein engineering of BCO by directed evolution (A), structure-based mutagenesis (B), d novo design of BCOs (C), optimization of metabolic pathway (MVA pathway, left; MEP pathway, right) for retinal production (top) through substrate channeling system (D), and co-factor regeneration system to increase the co-factor levels (E). Abbreviation for the compounds: G-3-P, glucose-3-phosphate; HMG-CoA, 3-hydroxy-3-methylglutaryl CoA; MVA, mevalonic acid; MVAP, phosphomevalonate; MVAPP, diphosphomevalonate; IPP, isopentenyl pyrophosphate; DMAPP, dimethylallyl pyrophosphate; GPP, geranyl pyrophosphate; FPP, farnesyl pyrophosphate; GGPP, geranylgeranyl pyrophosphate; DXP, 1-deoxy-d-xylulose-5-phosphate; MEP, methylerythritol phosphate; CDP-ME, 4-diphosphocytidyl-2-C-methyl-d-erythritol; CDP-ME2P, 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate; MECDP, 2C-methyl-d-erythritol 2,4-cyclodiphosphate; HMBPP, 1-hydroxy-2-methyl-2-butenyl 4-diphosphate. The genes encode the following enzymes: atoB/phaA, acetoacetyl-CoA synthase; mvaS, HMG-CoA synthase; mvaA, HMG-CoA reductase; mvaK1, mevalonate kinase; mvaK2, phosphomevalonate kinase; mavD, mevalonate-5-diphosphate decarboxylase; idi, IPP isomerase; ispA, FPP synthase; crtE, GGPP synthase, crtB, phytoene synthase; crtI, phytoene desaturase; crtY, lycopene cyclase; BCO1, β-carotene 15,15′-oxygenase; BCO2, β-carotene 9,10′-oxygenase; dxs, 1-deoxy-d-xylulose-5-phosphate synthase; dxs, 1-deoxy-d-xylulose-5-phosphate reductoisomerase; cms, 4-diphosphocytidyl-2C-methyl-d-erythritol synthase, mecps, 2C-methyl-d-erythriol-2,4-cyclodiphosphate synthase. Dashed arrow indicates multi-enzymatic steps.