Random Sequences May Have Putative Beta Lactamase Properties.

Citation: Kwek, BZN, Ardhanari-Shanmugam, KD, Woo, JH, Usman, S, Chua, JW, B, V, Shahrukh, K, Thong-Ek, C, Ling, MHT. 2019. Random Sequences May Have Putative Beta-Lactamase Properties. Acta Scientific Medical Sciences 3(7): 113-117.

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Beta-lactamases, which confer resistance to beta-lactam antibiotics, is of medical and healthcare concerns globally. Studies had placed the emergence of beta-lactamases to more than 2 billion years ago. However, it is not known where the first beta-lactamase originate. In this study, we examine the probability of de novo emergence of putative beta-lactamase from random sequences. A set of 10 thousand randomly generated sequences were aligned using Smith-Waterman algorithm and Needleman-Wunsch algorithm to a set of known class D beta-lactamases isolated from GenBank to determine the probability of each randomly generated sequence as putative beta-lactamases. Our results suggest that substantial proportion of randomly generated sequences may be putative beta-lactamases, with 4% of the randomly generated sequences showing 99% probability as putative beta-lactamases. To test whether a putative beta-lactamase can evolve over generations to have more characteristics of known beta-lactamases, in silico evolution was carried out using DOSE, an evolution simulation software. Our simulation results also suggest that a putative beta-lactamase may rapidly evolve into a more functional beta-lactamase under selection. Hence, de novo origination of beta-lactamase from random sequences is plausible.