foods Article One-Pot Synthesis of Lactose Derivatives from Whey Permeate Maryam Enteshari and Sergio I. Martínez-Monteagudo * Dairy and Food Science Department, South Dakota State University, Alfred Dairy Science Hall, Brookings, SD 57007, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-605-688-4118 Received: 17 May 2020; Accepted: 5 June 2020; Published: 13 June 2020 Abstract: The simultaneous production of lactulose (LAU), lactobionic acid (LBA), and organic acids from sweet and acid whey permeate (SWP and AWP) via catalytic synthesis (5% Ru/C) was studied in a continuous stirred-tank reactor. At selected conditions (60 ◦C, 60 bar, and 600 rpm), a maximum conversion of lactose (37 and 34%) was obtained after 90 min for SWP and AWP, respectively. The highest yield calculated with respect to the initial concentration of lactose for LAU was 22.98 0.81 ± and 15.29 0.81% after only 30 min for SWP, and AWP, respectively. For LBA, a maximum yield was ± found in SWP (5.23%) after 210 min, while about 2.2% was found in AWP. Six major organic acids (gluconic, pyruvic, lactic, formic, acetic, and citric acid) were quantified during the one-pot synthesis of lactose. Keywords: one-pot synthesis; catalysis; lactulose; lactobionic acid 1. Introduction Whey is the main byproduct obtained from the manufacture of cheese, yogurt, and milk protein concentrates [1]. It is the yellowish liquid separated from curds, and it is mainly made of water (~94%), lactose (~5%), proteins (~1%), minerals (~1%), and milk fat (~0.5%) [2]. As a byproduct, whey is concentrated and further fractionated to produce a wide array of products and ingredients with food and pharmaceutical applications. Examples of ingredients derived from whey are milk serum protein concentrate, whey powder, whey protein concentrate, whey protein hydrolysate, and whey protein isolate. Manufacturing details on the production of milk protein ingredients can be found elsewhere [3,4]. Over the last few years, the number of food formulations containing milk proteins has considerably increased due to the functional and nutritional properties of milk proteins [5]. Nowadays, products such as sport drinks, desserts, beverages, snacks, dietary, and weight management supplements are formulated with milk proteins. Overall, the manufacture of concentrates of milk proteins involves numerous unit operations, such as thermal treatment, selective fractionation, concentration, and drying. Selective fractionation by means of membrane technology is the key processing step in which the protein fraction is sequentially separated from the whey stream. The separation is performed by multiple filtration stages, where the proteins are concentrated in the retentate, while lactose and minerals are concentrated in permeate stream. The byproduct derived from the production of milk proteins is known as whey permeate, and it contains a considerable amount of lactose (75–80% on dry basis). Lactose (LA) presents technological challenges, such as poor solubility and low sweetness index, as well as malabsorption by a certain population, which has limited its further utilization [6]. Consequently, there is a considerable industrial interest to further utilize LA as a feedstock for the production of lactose-based ingredients [7,8]. As a feedstock, lactose has the potential to undergo Foods 2020, 9, 784; doi:10.3390/foods9060784 www.mdpi.com/journal/foods Foods 2020, 9, x FOR PEER REVIEW 2 of 11 Foods 2020, 9, 784 2 of 11 production of lactose-based ingredients [7,8]. As a feedstock, lactose has the potential to undergo differentdifferent reactions reactions leading leading to the formation of value-addedvalue-added compounds. Figure Figure 11 illustratesillustrates thethe simultaneoussimultaneous formation formation of of lactulose lactulose (LAU) (LAU) and and lactobionic lactobionic acid acid (LB (LBA),A), two two of of the the most most versatile versatile lactoselactose-derived-derived ingredients ingredients,, with with applications applications in in food, food, dairy, dairy, and pharmaceutical formulations. FigureFigure 1 1.. ReactionReaction pathway pathway for for the the formation formation of of lactulose lactulose and and lactobionic lactobionic acid acid via via isomerization isomerization and and dehydrogenation,dehydrogenation, respective respectively.ly. β d d LactuloseLactulose (4 (4--OO--β-D- --galactopyranosyl-galactopyranosyl-D--fructofuranose),fructofuranose), an an isomer isomer of of LA, LA, is is a a disaccharide disaccharide mademade of of galactose galactose and and fructose. fructose. It It is is used used in in the the treatment treatment of of hepatic hepatic encephalopathy encephalopathy and and chronic chronic constipationconstipation [9]. [9]. Industrially, Industrially, LAU LAU is is synthesized synthesized by by either either hom homogenousogenous catalysis catalysis under under alkaline alkaline conditionsconditions,, or or by by enzymatic synthesis using glycosyltransferases and glycosidases [[10].10]. Reaction Reaction schemesschemes and and conditions conditions for for LAU LAU synthesis synthesis can can be be found found elsewhere elsewhere [11]. [11 On]. Onthe theother other hand, hand, LBA LBA (4- β d O(4--βO-galactopyranosyl- -galactopyranosyl--D-gluconi-gluconicc acid) acid) is isan an aldonic aldonic acid acid or or sugar sugar-acid-acid made made up up of of galactose galactose linked linked toto a a gluconic gluconic acid acid [12]. [12]. The The LBA LBA molecule molecule has has various various functionalities functionalities,, such such as as antioxidant, antioxidant, chelating, chelating, andand humectant humectant,, arising arising from from the the high high number number of of hydroxyl hydroxyl groups. groups. The The partial partial oxidatio oxidationn of of LA LA results results inin the the formation formation of of LBA, LBA, where where the the aldehyde aldehyde group group is is converted converted into into its its corresponding corresponding carbonyl carbonyl groupgroup via via selective selective oxidation oxidation [13]. [13]. Most Most of ofthe the LBA LBA commercialized commercialized in inthe the world world is produced is produced via via1) biocatalytic1) biocatalytic conversion conversion using using dehydrogenase dehydrogenase or or oxidoreductase, oxidoreductase, or or 2) 2) heterogeneous heterogeneous catalysis catalysis using using Pd,Pd, Pt, Pt, or or Ru Ru as as insoluble insoluble catalysts. catalysts. The The m manufacturinganufacturing methods methods of of LBA LBA can can be be found found elsewhere elsewhere [12]. [12]. OneOne common common strategy employedemployed inin the the industrial industrial production production of of lactose-derived lactose-derived ingredients ingredients is the is theuse use of purifiedof purified lactose lactose (monohydrate (monohydrate or pharmaceuticalor pharmaceutical grade) grade) as aas feedstock, a feedstock, which which minimizes minimizes the theformation formation of secondary of secondary products. products. Fundamentally, Fundamentally, such a strategysuch a strategy aims to produceaims to aproduce single compound a single compoundvia multi-step via multi flow,- involvingstep flow, theinvolving formation, the formation, separation, separation, and isolation and isola of secondarytion of secondary and primary and primaryproducts. products. Alternatively, Alternatively, the conversion the conversion of lactose of through lactose one-pot through synthesis one-pot representssynthesis represents an innovative an innovativeutilization ofutilization lactose. One-pot of lactose. conversion One-pot involves conversion the synthesis involves of a mixturethe synthesis of compounds of a mixture that can of be compoundsused with minimal that can separation be used in with the finalminimal formulation. separation This in has the been final exemplified formulation. by our This group, has wherebeen exemplifieda sweetening by syrup our group, from aqueous where a lactose sweetening was produced syrup from via aqueous one-pot synthesislactose was (enzymatic produced hydrolysis via one- potfollowed synthesis by catalytic(enzymatic isomerization) hydrolysis followed [14,15]. Similarly,by catalytic Zaccheria isomerization) [16] produced [14,15]. aSimilarly, mixture ofZaccheria sorbitol [16]and dulcitolproduced from a lactosemixture via of one-pot sorbitol catalytic and dulcitol conversion. from Gallezot lactose [via17] conceptualizedone-pot catalytic and conversion. exemplified Gallezotthe production [17] conceptualized of a pool of molecules and exemplified from biomass the production via one-pot of a catalytic pool of synthesis.molecules Underfrom biomass the one-pot via oneapproach,-pot catalytic the high synthesis. concentration Under ofthe lactose one-pot present approach, in whey the permeatehigh conce canntration be used of lactose as an inexpensive present in wheyfeedstock permeate for a varietycan be used of chemical as an inexpensive modifications, feedstock such as for hydrogenation, a variety of chemical isomerization, modifications and oxidation., such as hydrogenation,During the catalytic isomerization, oxidation and of lactose,oxidation. the first products formed are LBA and LAU, followed by 2-keto-lactobionicDuring the catalytic acid as oxidation a secondary of lactose, product the [18 first]. Preliminary products formed results are showed LBA and that LAU, increasing followed the byoxygen 2-keto pressure-lactobionic improved acid as the a yieldsecondary of