{Reference Type}: Journal Article
{Title}: Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation.
{Author}: Liao Y;Wang XJ;Ma GL;Candra H;Qiu En SL;Khandelwal S;Liang ZX;
{Journal}: Chembiochem
{Volume}: 25
{Issue}: 1
{Year}: 2024 01 2
{Factor}: 3.461
{DOI}: 10.1002/cbic.202300590
{Abstract}: Octacosamicin A is an antifungal metabolite featuring a linear polyene-polyol chain flanked by N-hydroxyguanidine and glycine moieties. We report here that sub-inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T . We identified the biosynthetic gene cluster (oca BGC) that encodes a modular polyketide synthase (PKS) system for assembling the polyene-polyol chain of octacosamicin A. Our analysis suggested that the N-hydroxyguanidine unit originates from a 4-guanidinobutyryl-CoA starter unit, while the PKS incorporates an α-hydroxyketone moiety using a (2R)-hydroxymalonyl-CoA extender unit. The modular PKS system contains a non-canonical terminal module that lacks thioesterase (TE) and acyl carrier protein (ACP) domains, indicating the biosynthesis is likely to employ an unconventional and cryptic off-loading mechanism that attaches glycine to the polyene-polyol chain via an intermolecular amidation reaction.