Discovery and synthetic applications of novel thermostable biocatalysts from extremophiles (meta)genomes

The search of novel thermostable biocatalysts is still highly important in the development of enzyme-based industrial processes. During the last few years, the development and improvement of sequence-based metagenomic approaches has permitted to overcome the frequently observed limitations in the cultivation of extremophiles under laboratory conditions. We have exploited this approach in the search of novel thermostable enzymes with useful synthetic applications, such as epoxide hydrolases[1-3] and amine transferases[4] from hot springs and other high-temperature ecosystems. In a complementary way, the use of activity-guided methods as an alternative discovery approach, such as enrichment cultures, led us to the identification of a novel broad scope thermostable ?-amino acid transaminase from a Meiothermus strain isolated in an Icelandic hot spring[5]. Recently, by mining selected (meta)genomes, novel extremophilic hydroxysteroid dehydrogenases, enzymes so far described only from gut and soil bacteria, have been described for the first time. The results obtained in the study of the synthetic application of these novel biocatalysts, with both steroidal[6] and non-steroidal[7,8] substrates, will be presented. References [1] E. E. Ferrandi et al., FEBS Journal, 282, 2879-2894 (2015), DOI: 10.1111/febs.13328. [2] E. E. Ferrandi, et al., ChemCatChem, 7, 3171-3178 (2015), DOI: 10.1002/cctc.201500608. [3] E. E. Ferrandi, et al., Front. Bioeng. Biotechnol., 6, 144 (2018), DOI: 10.3389/fbioe.2018.00144. [4] E. E. Ferrandi, et al., Appl. Microbiol. Biotechnol., 101, 4963-4979 (2017), DOI: 10.1007/s00253-017-8228-2. [5] E. E. Ferrandi, et al., Biotechnol. J., 15, 2000125 (2020), DOI: 10.1002/biot.202000125. [6] S. Bertuletti, et al., ChemCatChem, accepted, "Biotrans 2021" Special Issue (2021). [7] S. Bertuletti, et al., Adv. Synth. Catal., 362, 2474-2485 (2020), DOI: 10.1002/adsc.202000120. [8] S. Bertuletti, et al., Eur. J. Org. Chem., 2021, 3992-3998 (2021), DOI: 10.1002/ejoc.202100174.