catalysts Article Selective Synthesis of Furfuryl Alcohol from Biomass-Derived Furfural Using Immobilized Yeast Cells Xue-Ying Zhang 1, Zhong-Hua Xu 1, Min-Hua Zong 1, Chuan-Fu Wang 2 and Ning Li 1,* 1 School of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China; [email protected] (X.-Y.Z.); [email protected] (Z.-H.X.); [email protected] (M.-H.Z.) 2 National Institute of Clean-and-Low-Carbon Energy, Future Science Park, Beijing 102211, China; [email protected] * Correspondence: [email protected] Received: 19 December 2018; Accepted: 6 January 2019; Published: 10 January 2019 Abstract: Furfuryl alcohol (FA) is an important building block in polymer, food, and pharmaceutical industries. In this work, we reported the biocatalytic reduction of furfural, one of the top value-added bio-based platform chemicals, to FA by immobilized Meyerozyma guilliermondii SC1103 cells. The biocatalytic process was optimized, and the tolerance of this yeast strain toward toxic furfural was evaluated. It was found that furfural of 200 mM could be reduced smoothly to the desired product FA with the conversion of 98% and the selectivity of >98%, while the FA yield was only approximately 81%. The gap between the substrate conversion and the product yield might partially be attributed to the substantial adsorption of the immobilization material (calcium alginate) toward the desired product, but microbial metabolism of furans (as carbon sources) made a negligible contribution to it. In addition, FA of approximately 156 mM was produced within 7 h in a scale-up reaction, along with the formation of trace 2-furoic acid (1 mM) as the byproduct. The FA productivity was up to 2.9 g/L/h, the highest value ever reported in the biocatalytic synthesis of FA. The crude FA was simply separated from the reaction mixture by organic solvent extraction, with the recovery of 90% and the purity of 88%. FA as high as 266 mM was produced by using a fed-batch strategy within 15.5 h. Keywords: biocatalysis; bio-based platform chemicals; furans; reduction; whole cells 1. Introduction Recently, the production of biofuels and bio-based chemicals from renewable biomass has attracted outstanding interest for reducing the dependence on fossil fuel sources, as well as mitigating global warming [1,2]. Like 5-hydroxymethylfurfural (HMF), furfural that can be synthesized readily from xylose is one of the “Top 10 + 4” bio-based platform chemicals [3–5]. There exist two active functional groups, including the aromatic ring and formyl group, in furfural, which are responsible for the high chemical reactivity of this bio-based molecule. Therefore, it can be upgraded readily into a group of value-added products via some typical chemical transformations such as reduction, oxidation, and Diels-Alder reactions [6]. Furfuryl alcohol (FA) is the most important derivative of furfural, since approximately 65% of furfural produced worldwide is utilized for the synthesis of FA [4,6]. FA has been used widely in polymer, food, and pharmaceutical industries [4,6]. FA is primarily used in the production of thermostatic resins, corrosion resistant fiber glass, and polymer concrete [7]. In addition, it is a building block in the manufacture of fragrances and pharmaceuticals, and for the Catalysts 2019, 9, 70; doi:10.3390/catal9010070 www.mdpi.com/journal/catalysts Catalysts 2019, 9, 70 2 of 13 Catalysts 2019, 9, x FOR PEER REVIEW 2 of 13 synthesisthe synthesis of useful of useful chemicals, chemicals, such such as tetrahydrofurfuryl as tetrahydrofurfuryl alcohol, alcohol, ethyl ethyl furfuryl furfuryl ether, ether, levulinic levulinic acid, andacid,γ and-valerolactone γ-valerolactone [6]. [6]. The industrial large-scale productionproduction of FA from furfural is performedperformed over Cu-based catalysts, especially Cu-Cr Cu-Cr catalysts, catalysts, in in gas gas or or liquid liquid phase phase [6]. [ 6Although]. Although the industrial the industrial routes routes have havebeen well- been well-established,established, they theysuffer suffer from from some some problems, problems, such such asas catalyst catalyst deactivation, deactivation, serious serious environmental environmental problems (due(due to to the the high high toxicity toxicity of chromium),of chromium and), overreductionand overreduction of the of desired the desired product product (thus leading (thus toleading the formation to the formation of 2-methylfuran of 2-methylfuran and furan) and [5,6, 8furan)]. To address [5,6,8]. theTo drawbacks,address the chemists drawbacks, have chemists devoted greathave effortsdevoted in great the last efforts decades. in the Significant last decades. advances Significant have been advances achieved have in thebeen chemical achieved catalytic in the hydrogenationchemical catalytic of furfuralhydrogenation to FA. Aof varietyfurfural of to new FA. chemicalA variety catalysts,of new chemical as well ascatalysts, efficient as reaction well as engineeringefficient reaction strategies, engineering have alsostrategies, been developedhave also been to improve developed the to production improve the of thisproduction commercially of this importantcommercially chemical important [4,6,9 chemical]. [4,6,9]. Biotransformation isis generally performed underunder mildmild conditions and is exquisitely selective, and biocatalysts areare environmentallyenvironmentally friendly friendly [10 [10].]. Hence, Hence, biocatalysis biocatalysis represents represents a promising a promising strategy strategy for upgradingfor upgrading bio-based bio-based furans furans such such as HMF as HMF and furfuraland furfural [11], [11], because because of the of inherent the inherent instability instability of these of chemicals.these chemicals. Nevertheless, Nevertheless, biocatalytic biocatalytic upgrading upgradin of theseg of these furans furans remains remains a great a great challenge, challenge, since since they arethey proverbial are proverbial inhibitors inhibitors against enzymes against andenzy microorganismsmes and microorganisms [12]. Previously, [12]. many Previously, microorganisms many (e.g.,microorganisms bacteria and (e.g., yeasts) bacteria were reportedand yeasts) to enable were report the detoxificationed to enable of the furfural detoxification into less toxicof furfural FA during into theless fermentationtoxic FA during of the biofuels fermentation and chemicals of biofuels from and lignocellulosic chemicals from hydrolysates lignocellulosic [13 hydrolysates–18]. However, [13– these18]. However, reported microbesthese reported exhibited microbes an unsatisfactory exhibited an furan unsatisfactory tolerance, andfuran the tolerance, biotransformation and the efficienciesbiotransformation were very efficiencies low, especially were very at low, moderate especially to high at moderate substrate to concentrationshigh substrate concentrations [19,20]. High substrate[19,20]. High concentrations substrate concentrations are highly desired are highly for achieving desired satisfactory for achieving productivities satisfactory in productivities the biocatalytic in synthesisthe biocatalytic of FA, synthesis which is of crucial FA, which for movingis crucial thesefor moving kinds these of green kinds technologies of green technologies toward and toward into successfuland into successful applications. applications. Recently, Recently, we isolated we isolatedMeyerozyma Meyerozyma guilliermondii guilliermondiiSC1103 SC1103 from from soil forsoil thefor reductionthe reduction of furans, of furans, including including HMF HMF and and furfural furfur [21al]. [21]. A chemo-enzymatic A chemo-enzymati methodc method was was reported reported for thefor the synthesis synthesis of FAof FA from from xylose xylose by by He’s He’s group group [22 [22,23],,23], in in which which the the intermediate intermediate furfuralfurfural derivedderived from xylosexylose was reduced into FA byby aa groupgroup ofof recombinantrecombinant EscherichiaEscherichia colicoli strains.strains. Interestingly, Interestingly, some E.E. colicoli strainsstrains exhibitedexhibited good good catalytic catalytic performances performances when when the the furfural furfural concentrations concentrations were were up up to 200–300to 200–300 mM mM[22 [22,23].,23]. Recently, Recently, Yan Yan et al. et reportedal. reported the the synthesis synthesis of FA of usingFA usingBacillus Bacillus coagulans coagulansNL01 NL01 [24]; the[24]; furfural the furfural tolerance tolerance of this bacteriumof this bacterium (less than (less 50 mM)than was50 mM) unsatisfactory, was unsatisfactory, although the although conversion the ofconversion 92% and theof 92% selectivity and the of selectivity 96% were of obtained. 96% were obtained. We recentlyrecently performedperformed preliminarypreliminary experiments in which furfural of 50 mM was reduced into FA by resting cells of of wild-type wild-type M.M. guilliermondii guilliermondii SC1103,SC1103, with with the the yield yield ofof 83% 83% and and the the selectivity selectivity of of96% 96% [21]. [21 To]. tap To the tap application the application potential potential of this of yeast this in yeast furfural in furfural reduction, reduction, the biocatalytic the biocatalytic process processwas optimized was optimized and reaction and reactionengineering engineering strategies strategies were applied. were applied.Additionally, Additionally, adaptively adaptively evolved evolvedyeast cells yeast entrapped cells entrapped in calcium in alginate calcium were alginate