In silico analysis of non-conventional gene targets for genetic interventions to enhance fatty acid production: a review.

Abstract

Since the 1990s, fatty acids (FA) have drawn significant industrial attention due to their diverse applications creating a demand for biological systems capable of producing high FA titers. While various strategies have been explored to achieve this, many of the conventional approaches rely on extensive genetic manipulations, which often result in strain instability, thus limiting its potential to yield better FA titers. Moreover, stresses such as pH, osmotic, and oxidative imbalances generated during FA production aggravate these challenges, further limiting FA titers. Under stress conditions, the cellular system responds by regulating stress-response proteins to bring about homeostasis. Recent findings suggest that transmembrane proteins, regulators of two-component systems, and cytoplasmic regulators can be strategically leveraged to address the problems related to stress-induced strain instability. Thus, non-conventional genetic targets, like chaperones (e.g., heat shock proteins) and DNA-binding transcriptional regulators (e.g., RcdA), which are not directly involved in FA metabolism, represent promising candidates to enhance strain stability and FA yields. Tools like Opt-Box and Weighted Gene Co-expression Network Analysis (WGCNA) serve as excellent platforms for understanding the cross-talk between these regulators and downstream enzymes. This review emphasizes the need for a shift towards identifying novel genetic targets by employing advanced in silico analysis and explains several molecular techniques that can aid in strain construction. Lastly, it discusses certain non-conventional gene targets that can help to overcome strain instability arising due to various stresses generated during/due to FA production.