Fig. 1: Modular de-regulation of central carbon metabolism drives carbon flux from xylose to 3-HP.

a Schematic overview of four metabolic modules. Module I is referred to as the 3-hydroxypropionic acid (3-HP) production module. The central carbon metabolism was divided into three distinct modules: the glycolysis module (II), the mitochondrial module (III), and the PDH bypass module (IV). To deregulate each module in the central carbon metabolism, five engineering strategies were employed: (1) controlling gene expression at the transcriptional level by a series of promoters characterized on xylose; (2) manipulating global transcription factors (TFs); (3) introducing heterologous proteins; (4) expressing mutated proteins; and (5) constructing biosensors. b The detailed implementations of the above mentioned five distinct engineering strategies in the various metabolism modules. BS binding sites, Enzymes and metabolites shown in the pathways: Mpc1/2/3 mitochondrial pyruvate carrier, PfkA and Pfk1/2 phosphofructokinase, FbaA and Fba1 fructose 1,6-bisphosphate aldolase, GpmA and Gpm1 phosphoglycerate mutase, PykA/F and Pyk1 pyruvate kinase, GapN NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, ACS acetyl-CoA synthetase, EutE acetaldehyde dehydrogenase, PO pyruvate oxidase, PTA phosphotransacetylase, KatE/G catalase-peroxidase, Acc1 acetyl-CoA carboxylase, MCR malonyl-CoA reductase, F-6-P fructose 6-phosphate, F-1,6-P fructose 1,6-bisphosphate, G-3-P Glyceraldehyde 3-phosphate, PEP phosphoenolpyruvic acid.