In silico study on the catalytic activity of lipase from Fusarium oxysporum f. sp. tracheiphilum in the bioconversion of Annonalide and its acylated derivatives

Abstract

This study presents an in silico investigation of the catalytic activity of lipase from the fungus Fusarium oxysporum f. sp. tracheiphilum. Researched was the biotransformation of the natural product Annonalide (1) and its semisynthetic derivatives 2 (O-acetyl), 3 (O-propanoyl), 4 (O-hexanoyl) and 5 (O-decanoyl) as a useful tool to explain the observed experimental results. Small-scale biotransformation of 1–5 using growing cells of the fungus revealed the influence of the O-acyl moiety in the substrate structure. Except for substrate 2, which was not biotransformed by the fungus, lipase-mediated hydrolysis of the O-acyl group was observed in substrates 3–5. Product (1 and Acrenol) formation varied with the O-acyl group length. The in silico study involved molecular docking to induce fit simulations, and molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) methods. These corroborated the preferential attack of Ser174 on the lactone ring (C19) of Annonalide (1), and the O-acyl side chain of substrates 2–5. Additionally, derivatives 3–5 were identified as the most suitable substrates to fit the active site of the lipase. All theoretical results agreed with the experimental observations, suggesting that increased acyl chain length favors lipase-mediated catalysis.