Enzymatic reactions involving the heteroatoms from organic substrates

Anais da Academia Brasileira de Ciências (2018) 90(1 Suppl. 1): 943-992 (Annals of the Brazilian Academy of Sciences) Printed version ISSN 0001-3765 / Online version ISSN 1678-2690 http://dx.doi.org/10.1590/0001-3765201820170741 www.scielo.br/aabc | www.fb.com/aabcjournal Enzymatic reactions involving the heteroatoms from organic substrates CATERINA G.C. MARQUES NETTO1,2, DAYVSON J. PALMEIRA1, PATRÍCIA B. BRONDANI3 and LEANDRO H. ANDRADE1 1 Departamento de Química Fundamental, Universidade de São Paulo, Avenida Prof. Lineu Prestes, 748, 05508-000 São Paulo, SP, Brazil 2 Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luis, s/n, Km 235, 13565-905 São Carlos, SP, Brazil 3 Departamento de Ciências Exatas e Educação, Universidade Federal de Santa Catarina, Rua João Pessoa, 2750, 89036-256 Blumenau, SC, Brazil Manuscript received on September 20, 2017; accepted for publication on January 1, 2018 ABSTRACT Several enzymatic reactions of heteroatom-containing compounds have been explored as unnatural substrates. Considerable advances related to the search for efficient enzymatic systems able to support a broader substrate scope with high catalytic performance are described in the literature. These reports include mainly native and mutated enzymes and whole cells biocatalysis. Herein, we describe the historical background along with the progress of biocatalyzed reactions involving the heteroatom(S, Se, B, P and Si) from hetero-organic substrates. Key words: heteroatom, biocatalysis, enzymes, biotransformation. INTRODUCTION Enzymes act as Nature’s machinery to obtain new molecules through energetically favorable reactions. This feature led chemists to incorporate enzymes in synthetic protocols to produce natural and unnatural heteroatom-containing organic molecules in an easier way for different purposes. Synthetic procedures involving the assimilation or transformation of heteroatom-containing molecules into organic compounds are common reactions employed in several organic (For recent reviews Correspondence to: Leandro Helgueira Andrade E-mail: * Contribution to the centenary of the Brazilian Academy of Sciences. see: Gao et al. 2015, Applegate and Berkowitz 2015, Guan et al. 2015, Wallace and Balskus 2014, Anobom et al. 2014, Fesko and Gruber-Khadjawi 2013, Matsuda 2013) or organometallic protocols (Bergbreiter and Momongan 1992, Gnedenkot and Ryabov 1994, Howell and Palin 1996, Rigby and Sugathapala 1996 and Ryabov et al. 1998). Therefore, it is evident that there is a demand for the synthesis of relevant hetero-organic derivatives, with special attention to environmental-friendly reactions, such as the biocatalyzed-transformations. The most common organic substrates for enzymes are alcohols (Goswami et al. 2013 and Somers et al. 1999), carbonylic compounds (Chang and Shaw 2009, Liederer and Borchardt 2006), phosphates (Konietzny and Greigner 2002, Servi An Acad Bras Cienc (2018) 90 (1 Suppl. 1) 944 CATERINA G.C. MARQUES NETTO et al. 1999), amines (Höhne and Bornscheuer 2009, Kohls et al. 2014) and amides (Boeriu et al. 2010, Gotor 1999). Considering the wide range of other elements present in Nature, only a modest number of biocatalytic applications have been developed (Schoemaker et al. 2003). In the field of catalysis, a high selectivity is not the sole target since a broad scope of substrates suitable for industrial application is often necessary (Lindbäck et al. 2014). In several cases, enzymes have high substrate specificity and catalytic efficiency (Demetrius 1998), which can give us an excellent opportunity in the search of new substrates for enzymatic catalysis. Enzymatic reaction of hetero-organic substrates can be subdivided in two main categories: the enzymatic transformation occurring at the heteroatom, and the enzymatic transformation occurring in any other functional group of the organic substrate. In general, the prior reaction involves oxidation/reduction of the heteroatom or change in bonding between the heteroatom and the organic moiety. In this review, enzymatic reactions involving the heteroatom from hetero-organic substrates are discussed. Figure 1 - Sulfur pathway in the metabolism of several organisms. An Acad Bras Cienc (2018) 90 (1 Suppl. 1) SULFUR Life depends on sulfur’s active redox chemistry. Therefore, sulfur constitutes an essential element found in amino acids and protein structures (Faloona 2009). The mechanism of its incorporation to organic molecules by several microorganisms and animals involves a prior reduction of sulfate to sulfide, followed by condensation with L -serine to produce L-cysteine (Ellis 1953). Particularly, L-cysteine is used for the production of methionine, coenzyme A and several other important thiols as shown in Figure 1a. Persulfidic sulfur (R-S-SH) is another sulfur species that also play an important role in life’s chemistry. These compounds provide an “active sulfur” able to undergo desulfuration reactions and to be transformed into FeS clusters, biotin, lipoic acid, thiamin, molybdopterin and thionucleosides, as shown in Figure 1b (Kessler 2006). The production of these important metabolic thiols and persulfidic species demands the action of enzymes. For example, penicillin biosynthesis requires condensation of cysteine, aminoadipic acid and valine. This process occurs in the ENZYMES FOR REACTIONS WITH UNNATURAL SUBSTRATES presence of isopenicillin N-synthase (Baldwin and Abraham 1988) with complete retention of configuration. In fact, such specific reactions normally compel unique catalysts and fortunately, metabolic proteins are found in all different classes of enzymes, such as oxidoreductases (Sellmann and Sutter 1996), hydrolases (Kiełbasiński 2011), transferases (Papenbrock et al. 2011), lyases (Broderick et al. 2014), isomerases (Lillig and Berndt 2013) and ligases (Hicks et al. 2007). Examples of these enzymes are everywhere in nature (Oae and Okuyama 1992) and chemists can seize these catalysts to perform an unlimited number of reactions, including oxidations, reductions, hydrolysis and the addition of new functional groups to a certain molecule. Here, we present some of the important contributions on organosulfur biocatalytic proccess. Other important aspects of sulfur biotransformation is described elsewhere (Colonna 1994, Deasy and Maguire 2014, Fernández and Khia 2003, Holland 1992, 2001, 1988, Kiełbasiński 2011, Matsui et al. 2014, O’Mahony et al. 2011). OXIDOREDUCTASES As previously stated, nature performs the conversion of sulfur containing molecules to produce important metabolites. An example of oxidoreductase acting on sulfur chemistry is NAD(P)H elemental sulfur oxidoreductase (NSR). This enzyme is able to reduce elemental sulfur to H2S (Schut et al. 2007). The mechanism of H2S synthesis involves the formation of di-, per-, and polysulfide derivatives of coenzyme A, as shown in Figure 2 (Herwald et al. 2013).This type of enzyme is responsible (...truncated)