Recombinant Idiomarina loihiensis (3R)-hydroxymyristoyl-[acyl-carrier-protein] dehydratase (fabZ)

Introduction

Idiomarina loihiensis is a marine bacterium known for its adaptation to deep-sea hydrothermal vent environments . I. loihiensis FabZ, or (3R)-hydroxymyristoyl-[acyl-carrier-protein] dehydratase, is an enzyme involved in fatty acid biosynthesis . FabZ catalyzes the dehydration of β-hydroxyacyl-ACP to trans-2-acyl-ACP, a crucial step in the elongation cycle of fatty acid synthesis .

Idiomarina loihiensis: A Deep-Sea Bacterium

Idiomarina loihiensis is a γ-proteobacterium initially isolated from hydrothermal vents on the Lō'ihi Seamount, Hawaii . This bacterium exhibits unique characteristics, including the ability to survive in a wide range of temperatures (4°C to 46°C) and salinities (0.5% to 20% NaCl) . Its genome comprises 2,839,318 base pairs, encoding 2,640 proteins . I. loihiensis has a distinctive fatty acid composition, characterized by a high percentage of iso-branched and saturated fatty acids, making it an interesting subject for studying lipid metabolism in extreme environments .

FabZ in Fatty Acid Biosynthesis

FabZ is a β-hydroxyacyl-acyl carrier protein (ACP) dehydratase that plays a vital role in the bacterial fatty acid biosynthesis (FAS) pathway . The FAS pathway is essential for synthesizing fatty acids, which are critical components of cell membranes and energy storage molecules . FabZ catalyzes the dehydration of β-hydroxyacyl-ACP to trans-2-acyl-ACP . This reaction is a key step in elongating the fatty acid chain .

Functional Studies of FabZ

In vitro studies have demonstrated the significance of FabZ in the fatty acid synthesis pathway . For instance, experiments involving E. coli have shown that increasing FabZ concentration markedly affects the steady-state kinetics of fatty acid synthesis . Specifically, a sixfold increase in activity was observed in a reconstituted system when FabZ concentration was more than 10-fold higher than other Fab enzymes . The highest activity achievable was 100 μM palmitic acid equivalents/min .

Inhibitors of FabZ

The development of inhibitors against FabZ has garnered interest, especially in the context of developing new antimicrobial drugs . Studies have identified inhibitors like NAS-91 and NAS-21 that prevent the binding of crotonoyl-CoA to PfFabZ in a competitive manner . These inhibitors have been shown to compromise the growth of P. falciparum and inhibit the parasite's fatty acid synthesis pathway .

Molecular Docking Investigations

Molecular docking analyses involving compounds like indolylbenzimidazole have been conducted to understand potential antibacterial action mechanisms . These investigations suggest interactions with targets like (p)ppGpp synthetases/hydrolases, FtsZ proteins, or pyruvate kinases .