ChemBioChem p. 550 - 563 (2020)
Update date:2022-08-05
Topics:
Eser, Bekir Engin
Poborsky, Michal
Dai, Rongrong
Kishino, Shigenobu
Ljubic, Anita
Takeuchi, Michiki
Jacobsen, Charlotte
Ogawa, Jun
Kristensen, Peter
Guo, Zheng
Enzymatic conversion of fatty acids (FAs) by fatty acid hydratases (FAHs) presents a green and efficient route for high-value hydroxy fatty acid (HFA) production. However, limited diversity was achieved among HFAs, to date, with respect to chain length and hydroxy position. In this study, two highly similar FAHs from Lactobacillus acidophilus were compared: FA-HY2 has a narrow substrate scope and strict regioselectivity, whereas FA-HY1 utilizes longer chain substrates and hydrates various double-bond positions. It is revealed that three active-site residues play a remarkable role in directing substrate specificity and regioselectivity of hydration. If these residues on FA-HY2 are mutated to the corresponding ones in FA-HY1, a significant expansion of substrate scope and a distinct enhancement in hydration of double bonds towards the ω-end of FAs is observed. A three-residue mutant of FA-HY2 (TM-FA-HY2) displayed an impressive reversal of regioselectivity towards linoleic acid, shifting the ratio of the HFA regioisomers (10-OH/13-OH) from 99:1 to 12:88. Notable changes in regioselectivity were also observed for arachidonic acid and for C18 polyunsaturated fatty acid substrates. In addition, TM-FA-HY2 converted eicosapentaenoic acid into its 12-hydroxy product with high conversion at the preparative scale. Furthermore, it is demonstrated that microalgae are a source of diverse FAs for HFA production. This study paves the way for tailor-made FAH design to enable the production of diverse HFAs for various applications from the polymer industry to medical fields.
View MoreShanghai Harvest Chemical Ind. Co., Ltd.
Contact:021-51385350
Address:ROOM 806-807, AI LI CHEN BUILDING, No.333 JINGXIANG ROAD, PUDONG DISTRICT, 201206, SHANGHAI
Shijiazhuang City Xiehe Pharmaceutical Co., Ltd
Contact:+86-311-80817929
Address:Shangzhuang,Shijiazhuang,China
Contact:0027-717-456976
Address:2ND FLOOR, 325 VAUSE ROAD, OVERPORT, 4001, SOUTH AFRICA
Sinoway International (Jiangsu) Co., Ltd.
Contact:+86-25-86630167
Address:17 Beijing Road (West), Nanjing, China
JIANGXI ZHANGFENG CHEMICAL CO., LTD.
Contact:+86-0799-3413066
Address:Xiyuan village, Xiabu Town, Xiangdong District
Doi:10.1021/jm00271a026
(1972)Doi:10.1139/v82-126
(1982)Doi:10.1021/ol0157095
(2001)Doi:10.1021/ol0100273
(2001)Doi:10.1039/b314883a
(2004)Doi:10.1021/om000226a
(2001)