Schematic overview of the relevant pathways of riboflavin production and engineering strategies for riboflavin production.
Bacillus subtilis gene names were bracketed. Dashed lines indicate multiple enzymatic steps. The bold lines indicate the overexpression of the corresponding genes. The × indicates the deletion of the corresponding genes. Enzymes encoded by the genes shown are: pgi, phosphoglucose isomerase; zwf, glucose 6-phosphate dehydrogenase; pgl, 6-phosphogluconolactonase; gnd, 6-phosphogluconate dehydrogenase; edd, phosphogluconate dehydratase; eda, multifunctional 2-keto-3-deoxygluconate 6-phosphate aldolase and 2-keto-4-hydroxyglutarate aldolase and oxaloacetate decarboxylase; ribA, GTP cyclohydrolase II; ribB, 3,4-dihydroxy-2-butanone 4-phosphate synthase; ribD, fused diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino)uracil reductase; ribE, 6,7-dimethyl-8-ribityllumazine synthase; ribC, riboflavin synthase; ribF, bifunctional riboflavin kinase/FMN adenylyltransferase; acs, acetyl-CoA synthetase. The abbreviated metabolic intermediates are: KDPG, 2-keto-3-deoxy-6-phospho-D-gluconate; GTP, guanosine-triphosphate; DARPP, 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate; ARPP, 5-amino-6-(5′-phosphoribitylamino)uracil; ArPP, 5-amino-6-(5-phospho-D-ribitylamino)uracil; ArP, 5-amino-6-(D-ribitylamino)uracil; DHPB, 3,4-dihydroxy-2-butanone-4-P; DRL, 6,7-dimethyl-8-(1-D-ribityl)lumazine; FMN, riboflavin-5'-phosphate; FAD, flavin adenine dinucleotide; TCA, Tricarboxylic acid cycle.