1. Introduction
Fatty acids play very important and diverse roles in living organisms,
such as signal transduction, energy management and maintaining
structural integrity to the normal metabolic process. Fatty acid
synthases (FAS) are widely found in prokaryotes and eukaryotes, although
their structures and functions vary. Fatty acids play a very important
role in keeping the metabolic functions normal and are primary
metabolites synthesized by a system of complex and tightly controlled
biosynthetic machinery (Liu et al ., 2010). Bacteria and plants
have type II FAS by which fatty acid synthesis is performed by a set of
individual enzymes (White et al ., 2005). Type I FAS, found in
animals and fungi, consist of huge molecular assemblies with separate
catalytic domains to stitch on the designated fatty acid synthesis, with
each catalytic domain acting as unique enzyme (Maier et al .,
2010; Wakil, 1989). In both type I and type II FAS, there is a common
acyl carrier protein (ACP) acting as the mobile domain, shuttling the
intermediate fatty acid substrates to various catalytic sites.
Studies have identified that FAS can be a promising drug target for
cancer (Chalbos et al., 1987; Kuhajda et al ., 1994; Migitaet al ., 2009; Vazquez-Martin et al ., 2008; Wang et
al ., 2004). Inhibition of FAS might lead to apoptosis of cancer cells
(Zhou et al ., 2003; Deepa et al ., 2013). Since FAS is
associated with mycolic acid biosynthesis it could be a TB drug target
(Bhatt et al., 2007), with low possibility of drug resistance and
toxicity due to the difference in the FAS systems of human and bacteria
(Gago et al ., 2011).
There are many molecules that target FAS, like Epigallocatechin,
Cerulenin, Orlistat, Pyrimidine, Triclosan, C75, CM55 etc., differing in
modes of action and eliciting severe side effects (Brusselmans et
al ., 2003; Moche et al ., 1999; Kridel et al ., 2004;
Loftus et al ., 2000; Liu et al ., 2002; Rendina et
al ., 2005; Tadao et al ., 1974). Hence, new FAS inhibitors are in
demand.
Marine microbial sources have become one of the major focuses of
research for identifying new chemical entities with diverse biological
activities. Cyanobacteria are known to produce molecules with diverse
pharmacological properties (Wijffels et al ., 2013; Dixit et
al ., 2013). In this study, a FAS inhibitor was successfully isolated
from the marine cyanobacteria, Phormidium ambiguum which could
form a lead molecule for drugs against many diseases ranging from cancer
to TB.