Table. 3.

Table. 3. Table 3

Folate overproduction in metabolically engineered strains

Microorganisms	Genetic engineering techniques	Results	Reference
Lactococcus lactis MG1363	Overexpression of folKE	Increasing the production of extracellular folate 8-fold (±10→±80 ng/mL)	Sybesma et al., 2003a
	Overexpression of folKE and folP	Increasing the production of extracellular folate 8-fold (±10→±80 ng/mL)
	Overexpression of folKE and folC	Increasing the production of extracellular 4-fold (±10→±40 ng/mL) and intracellular folate 3-fold (±50→±150 ng/mL)
	Overexpression of folA	There is no increase in extracellular folate production, and intracellular folate production decreases 2-fold (±75→±35 ng/mL)
Lactococcus lactis NZ9000	Cloning and expression of the hgh gene (human γ-glutamyl hydrolase)	Increasing the production of extracellular folate 6-fold (±10→±60 ng/mL)	Sybesma et al., 2003c
Lactococcus lactis NZ9000	Overexpression of PABA genes (pabA and pabBC)	There is no increase in folate production	Wegkamp et al., 2007
	Overexpression of PABA and folate genes (folB, folP, folKE, folQ, folC)	Increasing the level of total folate (91.7→2,700 ng/mL)
Ashbya gossypii ATCC 10895	Overexpression of AgFOL1 and AgFOL3; or overexpression of AgFOL1 and AgFOL2	Increasing the level of total folate up to approximately 2.5-fold	Serrano-Amatriain et al., 2016
Ashbya gossypii ATCC 10895	Overexpression of AgFOL2 and AgFOL3	Increasing the level of total folate up to 11-fold
	Overexpression of AgFOL1, AgFOL2, and AgFOL3	Increasing the level of total folate up to 16-fold (680 ng/mL)
	Deletion of AgMET7 (FPGS)	Increasing the level of total folate up to 5.7-fold (292.15 ng/mL), with the increasing proportions of extracellular folate ±30%
	Repression of AgRIB1 (GTP cyclohydrolase II)	Increasing the level of total folate up to 4.2-fold
	Deletion of ADE12 (adenylosuccinate synthase)	Decreasing the level of total folate
	Deletion of ADE12 and AgMET7	Increasing the level of total folate up to 11.9-fold
	Overexpression of AgFOL1, AgFOL2, and AgFOL3; and deletion of ADE12	Increasing the level of total folate up to 15-fold (677 ng/mL)
	Overexpression of AgFOL1, AgFOL2, and AgFOL3; repression of AgRIB1; and deletion of ADE12	Increasing the level of total folate up to 21-fold (964 ng/mL)
	Overexpression of AgFOL1, AgFOL2, and AgFOL3; deletion of AgMET7 and ADE12	Increasing the level of total folate up to 51-fold (2,000 ng/mL)
	Overexpression of AgFOL2 and AgFOL3; deletion of AgMET7 and ADE12; and repression of AgRIB1	Increasing the level of total folate up to 146-fold (6,595 ng/mL)
Bacillus subtilis 168	Deletion of yitJ	There is no increase in folate production	Yang et al., 2020
Bacillus subtilis 168	Deletion of yitJ; cloning and overexpression of metF	Increasing the production of 5-MTHF 22.3-fold (10.28→229.62 ng/mL)	Yang et al., 2020
	Deletion of yitJ and purU; and overexpression of metF	Increasing the production of 5-MTHF 24.3-fold (10.28→250 ng/mL)
	Deletion of yitJ and purU; and overexpression of metF and dfrA	Increasing the production of 5-MTHF 26.4-fold (10.28→271.64 ng/mL)
	Deletion of yitJ and purU; and overexpression of metF, dfrA, and folC	Increasing the production of 5-MTHF 38.9-fold (10.28→±400 ng/mL)
	Deletion of yitJ and purU; and overexpression of metF, dfrA, folC, and pabB	Increasing the production of 5-MTHF 38.9-fold (10.28→±400 ng/mL)
	Deletion of yitJ and purU; and overexpression of metF, dfrA, folC, pabB, and folE	Increasing the production of 5-MTHF 48.6-fold (10.28→±500 ng/mL)
	Deletion of yitJ and purU; and overexpression of metF, dfrA, folC, pabB, folE, and yciA	Increasing the production of 5-MTHF 93.4-fold (10.28→960.27 ng/mL)
	Deletion of yitJ and purU; overexpression of metF, dfrA, folC, pabB, folE, and yciA; and repression of panB3	Increasing the production of 5-MTHF 124.5-fold (10.28→1,280 ng/mL)
	Deletion of yitJ and purU; overexpression of metF, dfrA, folC, pabB, folE, and yciA; and repression of thyA1	Increasing the production of 5-MTHF 135.2-fold (10.28→1,390 ng/mL)
	Deletion of yitJ and purU; overexpression of metF, dfrA, folC, pabB, folE, and yciA; and repression of pheA1	Increasing the production of 5-MTHF 140-fold (10.28→1,440 ng/mL)
	Deletion of yitJ and purU; overexpression of metF, dfrA, folC, pabB, folE, and yciA; and repression of trpE3	Increasing the production of 5-MTHF 145-fold (10.28→1,490 ng/mL)
	Deletion of yitJ and purU; overexpression of metF, dfrA, folC, pabB, folE, and yciA; and repression of pheA2	Increasing the production of 5-MTHF 154-fold (10.28→1,584.34 ng/mL)
Lactococcus lactis NZ9000	Overexpression of metF	Increasing the production of intracellular 5-MTHF up to 18 ng/mL	Lu et al., 2019
	Overexpression of dfrA	There is no increase in folate production
	Overexpression of thyA	There is no increase in folate production
	Overexpression of glyA	There is no increase in folate production
	Overexpression of folD	There is no increase in folate production
	Overexpression of metF and dfrA	Increasing the production of intracellular 5-MTHF up to ±30 ng/L
	Overexpression of metF and glyA	Increasing the production of intracellular 5-MTHF up to ±33 ng/L
	Overexpression of metF and thyA	Increasing the production of intracellular 5-MTHF up to ±23 ng/L
	Overexpression of metF, glyA, and folE	Increasing the production of intracellular 5-MTHF up to ±50 ng/L
	Overexpression of metF, dfrA, and folE	Increasing the production of intracellular 5-MTHF up to ±73 ng/L
	Overexpression of metF, dfrA, folE, and the G6PDH gene	Increasing the production of intracellular 5-MTHF up to ±100 ng/L
	Overexpression of metF, dfrA, folE, the G6PDH gene, and fau	Increasing the production of intracellular 5-MTHF up to ±132 ng/L

Prev Nutr Food Sci 2023;28:386~400 https://doi.org/10.3746/pnf.2023.28.4.386