40421-51-0Relevant articles and documents
Stereoselective Two-Step Biocatalysis in Organic Solvent: Toward All Stereoisomers of a 1,2-Diol at High Product Concentrations
Wachtmeister, Jochen,Jakoblinnert, Andre,Rother, D?rte
, p. 1744 - 1753 (2016)
Biotransformations on larger scale are mostly limited to cases in which alternative chemical routes lack sufficient chemo-, regio-, or stereoselectivity. Here, we expand the applicability of biocatalysis by combining cheap whole cell catalysts with a microaqueous solvent system. Compared to aqueous systems, this permits manifoldly higher concentrations of hydrophobic substrates while maintaining stereoselectivity. We apply these methods to four different two-step reactions of carboligation and oxidoreduction to obtain 1-phenylpropane-1,2-diol (PPD), a versatile building block for pharmaceuticals, starting from inexpensive aldehyde substrates. By a modular combination of two carboligases and two alcohol dehydrogenases, all four stereoisomers of PPD can be produced in a flexible way. After thorough optimization of each two-step reaction, the resulting processes enabled up to 63 g L-1 product concentration (98% yield), space-time-yields up to 144 g L-1 d-1, and a target isomer content of at least 95%. Despite the use of whole cell catalysts, we did not observe any side product formation of note. In addition, we prove that, by using 1,5-pentandiol as a smart cosubstrate, a very advantageous cofactor regeneration system could be applied.
A two-step biocatalytic cascade in micro-aqueous medium: Using whole cells to obtain high concentrations of a vicinal diol
Jakoblinnert, Andre,Rother, Doerte
, p. 3472 - 3482 (2014)
Although single- and multi-step biocatalytic approaches show persuasive advantages for the synthesis of especially chiral compounds (e.g. high chemo- and stereoselectivity), their application often suffers from low substrate loads and hence low space-time-yields. We herein present a synthetic cascade approach in which lyophilised, recombinant whole cells are applied in micro-aqueous reaction systems yielding extremely high space-time-yields. As an example we investigated the two-step synthesis of 1-phenylpropane-1,2-diol starting from cheap aldehydes and achieved high selectivities (ee/de > 99%) and high product concentrations. The new concept of running biocatalytic cascades in a mixture of high substrate loads and organic solvents under addition of small amounts of highly concentrated buffer is not only very easy-to-apply, but also exhibits several economic and ecologic advantages. On the one hand the usage of whole, lyophilised cells circumvents time-consuming enzyme purification as well as addition of expensive cofactors (here ThDP and NADPH). Additionally, catalyst and product workup is facilitated by the application of organic solvents (here MTBE). On the other hand, the employment of whole cells very effectively circumvents stability problems of biocatalysts in unconventional media enabling the addition of extremely high substrate loads (up to 500 mM in our example) and is therefore an easy and effective approach for multi-step biocatalysis. After optimisation, the combination of a carboligation step followed by a second oxidoreduction step with whole cell catalysts afforded an efficient two-step cascade for the production of 1-phenylpropane-1,2-diol with space-time yields up to 327 g L-1 d-1 and an E-factor of 21.3 kg waste kgproduct-1. This journal is the Partner Organisations 2014.
Modularized Biocatalysis: Immobilization of Whole Cells for Preparative Applications in Microaqueous Organic Solvents
Wachtmeister, Jochen,Mennicken, Philip,Hunold, Andreas,Rother, D?rte
, p. 607 - 614 (2016)
The use of whole-cell biocatalysts enables catalyst application in microaqueous reaction systems, in which the liquid phase consists of high substrate loadings in organic solvents, to enable access to high concentrations of easy-to-purify product. One current research focus is the modularization of single reaction steps to (i)enable flexible combinations into multi-step enzyme reactions, (ii)investigate ideal reaction conditions, and (iii)facilitate catalyst handling and recycling. Therefore, we published the easy-to-apply encapsulation of a lyophilized whole-cell catalyst in a polymeric membrane recently. These catalytic "teabags" were demonstrated to enable flexible catalyst combinations for multi-step reactions and excellent recyclability during repeated batch experiments. We now describe the applicability of these "teabags" on a larger scale by using the new SpinChem reactor and a classical stirred-tank reactor model. As an alternative, we investigate the described alginate entrapment approach and compare the results. The carboligation reaction towards (R)-benzoin, using lyophilized E.coli that enclose Pseudomonas fluorescens benzaldehyde lyase (EC 4.1.2.38), served as a model reaction. It was demonstrated that the catalytic "teabags" are scalable and perform equally on the investigatory 5mL scale and the preparative 140mL reactor scale. Tested in a more advanced application, the "teabags" were proven to be useful in a one-pot two-step reaction for the gram-scale production of 1-phenylpropane-1,2-diol by using the SpinChem reactor, which allowed to reach an industrially relevant product concentration (32.9g L-1) and space-time yield (8.2g L-1 d-1).
Enzymatic synthesis of all stereoisomers of 1-phenylpropane-1,2-diol
Kihumbu,Stillger,Hummel,Liese
, p. 1069 - 1072 (2002)
A stereoselective two-step enzymatic synthesis of all four stereoisomers of 1-phenylpropane-1,2-diol starting from benzaldehyde and acetaldehyde is described. By using one of four possible combinations of a lyase followed by an alcohol dehydrogenase, each diol is accessible separately.
Synthesis of α-hydroxy ketones and vicinal (R, R)-diols by Bacillus clausii DSM 8716T butanediol dehydrogenase
Bongaerts, Johannes,Jablonski, Melanie,Kipp, Carina Ronja,Molinnus, Denise,Muschallik, Lukas,Pohl, Martina,Sch?ning, Michael J.,Selmer, Thorsten,Siegert, Petra,Wagner, Torsten
, p. 12206 - 12216 (2020/04/20)
α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716T (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn2+ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.
Regio- and stereoselective multi-enzymatic aminohydroxylation of β-methylstyrene using dioxygen, ammonia and formate
Corrado, Maria L.,Knaus, Tanja,Mutti, Francesco G.
supporting information, p. 6246 - 6251 (2019/12/03)
We report an enzymatic route for the formal regio- and stereoselective aminohydroxylation of β-methylstyrene that consumes only dioxygen, ammonia and formate; carbonate is the by-product. The biocascade entails highly selective epoxidation, hydrolysis and hydrogen-borrowing alcohol amination. Thus, β-methylstyrene was converted into 1R,2R and 1S,2R-phenylpropanolamine in 59-63% isolated yields, and up to >99.5 : 0.5 dr and er.
