Table 6.
Effects of different metabolic engineering strategies and chassis on improving the production of NMN.
| Substrates | Strategies | Enzyme source | Pathways | Chassis | NMN production | References |
|---|---|---|---|---|---|---|
| Nicotinamide (NAM) | Knockout of nadR | L. latis NZ9000 | Salvage pathway | L. latis NZ9000 | ~0.2 g L−1 mg−1 protein | Kong et al. (2023) |
| NAM | Overexpression of FtnadE* | FtnadE from F. tularensis | Salvage pathway | L. latis NZ9000ΔnadR | 0.765 g L−1mg protein | Kong et al. (2023) |
| Glucose, fructose | Fermentation | — | — | F. tropaeoli RD011727 | 1.5× 10−3 g L−1 | Sugiyama et al. (2021) |
| Glucose, fructose | Fermentation | — | — | F. durionis RD012353 | ~2 × 10−3 g L−1 | Sugiyama et al. (2021) |
| NAM, lactose | Overexpression of nampt and PRS135I | nampt gene from Haemophilus ducreyi and PRS135I from Bacillus amyloliquefaciens with L135I mutation | Salvage pathway | E. coli BL21(DE3) pLysS | 1.726 10−2 g L−1 protein | Marinescu et al. (2018) |
| Nicotinic acid (NA) | Overexpression of nadV | nadV gene from Ralstonia solanacearum | Salvage pathway | E. coliΔpncC | — | Black et al. (2020) |
| NA | Overexpression of nadV and FtnadE | nadV gene from R. solanacearum and FtnadE from F. tularensis | Salvage pathway | E. coliΔpncC | ~0.5 g L−1 | Black et al. (2020) |
| NAM, glucose | Overexpression of nampt, PRS135I, zwf, gnd, and YgcS; deletion of pncC, yeeP, yjiV, yeeL, and nadR | nampt gene from H. ducreyi; PRS135I from B. amyloliquefaciens with L135I mutation; zwf, gnd, and YgcS from E. coli MG1655 | Salvage pathway | E. coli MG1655 (NMN07-YgcS) | ~0.3 g L−1 | Liu et al. (2021) |
| NAM, glucose | Overexpression of ado1; deletion of amn with optimized condition | ado1 gene from Saccharomyces cerevisiae | Salvage pathway | E. coli NMN07Δamn: P119-ado1 | 0.4962 g L−1 | Liu et al. (2021) |
| Ribose, NAM | Overexpression of nampt-prs1-prs2 | nampt, prs1 and prs2 from Homo sapiens | Salvage pathway | E. coli BL21(DE3) | 0.772 g L−1 | Maharjan et al. (2021) |
| NAM, glucose | Overexpression of nampt, niaP, pnuC, pgi, zwf, pgl, gnd, rpiA, rpiB, and prs | nampt gene from Chitinophaga pinensis; niaP from Burkholderia cenocepacia; pnuC from Bacillus mycoides | Salvage pathway | E. coli BL21(DE3) | 6.79 g L−1 | Shoji et al. (2021) |
| NAM | Overexpression of VpnadV, BaPRSL135I, and BMpnuC in a shake flask | VpnadV gene from Vibrio bacteriophage KVP40; PRS135I from B. amyloliquefaciens with L135I mutation; BMpnuC from B. mycoides | Salvage pathway | E. coli BL21(DE3) | 2.6 g L−1 | Huang et al. (2022) |
| NAM | Overexpression of VpNadV, BaPRSL135I, and BMpnuC in a 5-L bioreactor | VpnadV from V. bacteriophage KVP40; PRS135I from B. amyloliquefaciens with L135I mutation; BMpnuC from B. mycoides | Salvage pathway | E. coli BL21(DE3) | 16.2 g L−1 | Huang et al. (2022) |
| None | Overexpression of nampt and BMpnuC | nampt gene from C. pinensis; pnuC from B. mycoides | Salvage pathway | E. coli BL21(DE3) | 0.24 g L−1 | Bi et al. (2023) |
| NAM, glucose | Overexpression of nampt, BMPnuC, zwf, gnd, prs, and ado1; Knockout of amn and add | nampt gene from C. pinensis; BMpnuC from B. mycoides; ado1 gene from S. cerevisiae; zwf, gnd, and prs gene from E. coli BL21(DE3) | Salvage pathway | E. coli BL21(DE3) | 1.1 g L−1 | Bi et al. (2023) |
| D-xylose, NAM | Overexpression of xylA, xylB, rpe, rpiA, rpiB, prs, and nampt; Knockout of hisG, hpt, apt, tktB/talA, talB, pncC, and nadR in the optimized system | nampt gene from C. pinensis; xylA, xylB, rpe, rpiA, rpiB, and prs from E. coli BL21(DE3) | Salvage pathway | E. coli BL21(DE3) | 0.4975 g L−1 | Su et al. (2024) |
| D-xylose, NAM | Overexpression of xylA, xylB, rpe, rpiA, rpiB, prs, and nampt; Knockout of hisG, hpt, apt, tktB/talA, talB, pncC, and nadR in the 5 L-bioreactor | nampt gene from C. pinensis; xylA, xylB, rpe, rpiA, rpiB, and prs from E. coli BL21(DE3) | Salvage pathway | E. coli BL21(DE3) | 0.7602 g L−1 | Su et al. (2024) |
| Glucose | Overexpression of pncB, nadE, and pnuC | pncB and nadE from Bacillus subtilis; pnuC from B. mycoides | de novo pathway | B. subtilis WB600 | 3.396 g L−1 | Tan et al. (2024) |
| Nicotinamide ribose, ATP | Overexpression of NRK | NRK from Homo sapiens | Salvage pathway | S. cerevisiae EBY100 | 12.6 g L−1 | He et al. (2022) |
| Aspartic acid | Overexpression of nadABC, nadDE, and MazG | nadABC, nadDE, and MazG gene from E. coli ATCC8739 | de novo pathway | E. coli 8,739(DE3) | 0.153 g L−1 | Wang P. et al. (2024) |
| Asp, NAM, glucose | Overexpression of nadABC, nadDE, MazG, nadV, niaP, pnuC, zwf, gnd, and prs | nadABC, nadDE zwf, gnd, and MazG gene from E. coli ATCC8739; nadV from C. pinensis, niaP from B. cenocepacia, and pnuC from B. mycoides; prs from P. calidifontis | Salvage pathway and de novo pathway | E. coli 8,739(DE3) | 0.781 g L−1 | Wang P. et al. (2024) |
ND, not determined; tktB, transketolase 2; talA, transaldolase A; talB, transaldolase B; amn, AMP nucleosidase; add, adenosine deaminase; ado1, adenosine kinase; xylA, xylose isomerase; xylB, xylulo-kinase; rpe, ribulose 3-phosphate isomerase; hisG, ATP phosphoribosylase; apt, adenine phosphoribosyl transferase; hpt, hypoxanthine-guanine phosphoribosyl transferase.