**1. Introduction**

Biotechnological valorization of lignocellulosic residues derived from the agro-industrial sector is of great importance in many countries with intense agriculture in order to deal with the increasing demand of the society for energy and materials, the mitigation of greenhouse gas emissions and waste production and the development of a bio-based circular economy [1]. For such a sustainable bio-based economy, biorefineries that provide integrated facilities to produce a wide range of bio-products and bioenergy from biomass residues within a zero waste approach are considered as main pillars [2]. Around 4.6 billion tonnes of lignocellulosic biomass are produced annually as agricultural residues worldwide, of which only about 25% are used intensively [3,4]. However, they could serve as cheap, renewable and widely available raw materials for biorefineries [5].

Wheat (*Triticum aestivum*) and rice (*Oryza sativa*) are considered the most important crops in the human diet by contributing about 20% and 19% of the average calorie intake at global level, respectively [6]. The current worldwide production of wheat and rice are estimated at around 760 and 500 million tonnes, respectively, by FAO [7,8]. Moreover, increased demands for wheat and rice in the near future are usually predicted [9,10]. Hence,

**Citation:** Bed˝o, S.; Fehér, A.; Khunnonkwao, P.; Jantama, K.; Fehér, C. Optimized Bioconversion of Xylose Derived from Pre-Treated Crop Residues into Xylitol by Using *Candida boidinii*. *Agronomy* **2021**, *11*, 79. https://doi.org/10.3390/ agronomy11010079

Received: 27 November 2020 Accepted: 29 December 2020 Published: 1 January 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

the intense cultivation and processing of these crops generate huge amount of lignocellulosic by-products having the potential to be valorized in biorefinery processes [10,11]. Wheat bran and rice straw are the main lignocellulosic by-products of wheat-milling and rice-harvesting processes, with an estimated global production of 150 and 730 million tonnes per year, respectively [12,13]. They contain a considerable amount of xylan-type hemicellulose fractions besides cellulose and lignin [14,15]. In an appropriate biorefinery process, the main constituents of the lignocellulosic raw material (cellulose, hemicellulose, lignin, protein etc.) can be sharply separated and converted into high-value platform chemicals, bio-products and energy [16]. Due to the relatively high xylan content of wheat bran and rice straw, one of the most promising platform chemicals that can be produced from them in a biorefinery is xylitol [17,18].

Xylitol is a five-carbon polyol that is mainly used in the food industry as an alternative sweetener. It has an equivalent sweetness to sucrose but with lower caloric value and glycemic index. It is an ideal sweetener for diabetics because its metabolism is independent of insulin [19,20]. Moreover, due to its other specific properties, it is extensively used in personal health products such as mouthwash and toothpaste [21]. It is also used in cosmetics and by the pharmaceutical industry as therapeutic or coating agents [22]. Xylitol is currently produced by the chemical reduction of xylose on an industrial scale. However, a high purity of xylose is required for the chemical reduction process to avoid the formation of by-products (e.g., arabitol). Thus an extensive xylose purification step is inevitable prior to the chemical reduction, which contributes to the high production cost of xylitol [23,24]. On the other hand, xylitol can be produced by a microbial process. The microbial reduction takes place under mild conditions (in terms of pressure and temperature), and it does not require highly pure xylose as a carbon substrate, thus allowing the direct utilization of hemicellulosic hydrolysates that contain a mixture of sugars [25]. There are several microorganisms among bacteria, yeasts, and fungi with the capability of producing xylitol, though, the most efficient species belong to yeasts of *Candida*, such as *C. tropicalis*, *C. guilliermondi*, and *C. boidinii* [26]. However, there are several factors (e.g., pH, temperature, aeration, initial substrate concentration, inoculum level, medium composition etc.) affecting the xylitol fermentation. Oxygen supply and initial substrate concentration are considered as critical variables [27,28]. For the efficient production of xylitol, yeasts usually require a so-called micro-aerobic condition, providing oxygen limitation during the xylitol formation phase of the fermentation. The aeration conditions are usually characterized by the oxygen transfer rate (OTR) or oxygen mass transfer coefficient (kLa) of the fermentation system applied. The optimal OTR for xylitol production strongly depends on the yeast strain and fermentation medium applied, so it has to be determined in every case. Moreover, it can be affected by other fermentation parameters as well. Interestingly, the possible interactions between the fermentation parameters affecting the xylitol production are poorly investigated in the literature on this topic. Many studies reported that high xylose concentration can strongly inhibit xylitol production [29,30]; however, possible explanations were usually only hypothesized. Further investigations on the effects of the initial substrate concentration and its interaction with other fermentation parameters are still required in order to provide a proper explanation of the phenomena. Xylose-rich, hemicellulosic hydrolysates derived from the pre-treatment or fractionation processes of lignocellulosic residues are promising raw materials for biotechnological xylitol production [31].

In this study, the effects of initial xylose concentration and aeration on the xylitol production of *Candida boidinii* were investigated and the xylitol production was optimised. In addition, xylose-rich hydrolysates derived from acidic pre-treatments of wheat bran and rice straw were characterized and tested in xylitol fermentation by *C. boidinii*. This study revealed the main factors affecting the xylitol production of *C. boidinii* and provided validated models to predict xylitol yield and productivity depending on the initial xylose concentration and OTR. Moreover, promising methods to obtain xylose-rich hydrolysates

from rice straw and wheat bran were selected and xylitol production under the most favorable conditions was successfully performed.
