US 12,435,348 B2
Microbial cells for spermidine production
Jiufu Qin, Virum (DK); Anastasia Krivoruchko, Gothenburg (SE); Florian David, Gothenburg (SE); and Jens Nielsen, Gothenburg (SE)
Assigned to CHRYSEA LIMITED, Dublin (IE)
Appl. No. 16/629,643
Filed by CHRYSEA LIMITED, Dublin (IE)
PCT Filed Jul. 13, 2018, PCT No. PCT/SE2018/050763
§ 371(c)(1), (2) Date Jan. 9, 2020,
PCT Pub. No. WO2019/013696, PCT Pub. Date Jan. 17, 2019.
Claims priority of application No. 1750933-2 (SE), filed on Jul. 14, 2017.
Prior Publication US 2020/0270654 A1, Aug. 27, 2020
Int. Cl. C12P 13/00 (2006.01); A23L 33/135 (2016.01); C07K 14/395 (2006.01); C12N 9/06 (2006.01); C12N 9/10 (2006.01); C12N 9/12 (2006.01); C12N 9/88 (2006.01)
CPC C12P 13/001 (2013.01) [A23L 33/135 (2016.08); C07K 14/395 (2013.01); C12N 9/0028 (2013.01); C12N 9/1077 (2013.01); C12N 9/1085 (2013.01); C12N 9/1096 (2013.01); C12N 9/1252 (2013.01); C12N 9/88 (2013.01); C12Y 105/0102 (2013.01); C12Y 204/02028 (2013.01); C12Y 205/01006 (2013.01); C12Y 205/01016 (2013.01); C12Y 205/01022 (2013.01); C12Y 206/01001 (2013.01); C12Y 207/07007 (2013.01); C12Y 401/0105 (2013.01); A23V 2002/00 (2013.01)] 22 Claims
 
1. A microbial cell capable of producing spermidine, wherein said microbial cell is genetically modified for overexpression of S-adenosylmethionine decarboxylase (EC 4.1.1.50) and spermidine synthase (EC 2.5.1.16); and for enhanced S-adenosylmethionine (SAM) biosynthesis by overexpression of at least one enzyme in the methionine salvage pathway selected from a group consisting of 5-methylthioribose-1-phosphate isomerase (MRI) (EC 5.3.1.23), methylthioribulose-1-phosphate dehydratase (MDE) (EC 4.2.1.109), 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase (EC 3.1.3.77), acireductone dioxygenase (EC 1.13.11.54), and branched-chain amino acid transaminase (BAT) (EC 2.6.1.5, EC 2.6.1.57, EC 2.6.1.42), wherein said microbial cell is genetically modified for attenuated activity of ornithine decarboxylase antizyme (OAZ) and ornithine carbamoyltransferase (OTC) (EC 2.1.3.3), or deletion or disruption of a gene encoding OAZ and a gene encoding OTC, wherein the at least one enzyme for enhanced SAM biosynthesis is overexpressed in an amount to produce an increased amount of spermidine compared to a corresponding microbial cell not overexpressing the at least one enzyme.