Chemical Science p. 5052 - 5057 (2020)
Update date:2022-08-25
Topics:
Cosgrove, Sebastian C.
Grogan, Gideon
Mangas-Sanchez, Juan
Marshall, James R.
Palmer, Ryan B.
Ramsden, Jeremy I.
Sharma, Mahima
Thorpe, Thomas W.
Turner, Nicholas J.
Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms fromNeosartoryaspp. (NfRedAm andNfisRedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as (R)-2-aminohexane in space time yields up to 8.1 g L?1h?1. The remarkable features ofNfRedAmand NfisRedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.
View MoreJinan Hongfangde Pharmatech Co.LTD
Contact:0531-88870908
Address:F Bldg,750#,Shunhua Rd,New&High-tech Zone,Jinan,Shandong,China 250101
Shanghai Yongyi Biotechnology Co., Ltd
Contact:+86-0512-69561955
Address:Suite 3005, City Gateway, No.398 North CaoXi Road, XuHui District, Shanghai 200030, China.
JIANGXI AIFEIMU TECHNOLOGY CO.,LTD
Contact:+86-570-6040289
Address:FINECHEMICAL PARK,ZIBU TOWN,WANNIAN COUNTY,JIANGXI PROV.,CHINA,ZIP
Shanghai Standard Biotech Co., Ltd.
Contact:+86-18502101150
Address:Room 103, Building 2nd, NO.720, Cailun Road , Pudong District, Shanghai, China
Hebei Lead Bio-Chemicals Co., Ltd.
website:http://www.ldbiochem.com
Contact:+86-311-87826503
Address:481, Heping West Road, Shijiazhuang,China
Doi:10.1111/j.1551-2916.2005.00582.x
(2005)Doi:10.1006/jcat.1998.2277
(1998)Doi:10.1021/acsmedchemlett.5b00107
(2015)Doi:10.1080/10426507.2019.1603720
(2019)Doi:10.3390/molecules21050607
(2016)Doi:10.1002/cctc.201500041
(2015)