The acyl carrier protein (ACP) is a cofactor of both fatty acid and polyketide biosynthesis machinery. It is one of the most abundant proteins in cells of E. coli. In both cases, the growing chain is bound to the ACP via a thioester derived from the distal thiol of a 4'-phosphopantetheine moiety.
Phosphopantetheine, also known as 4'-phosphopantetheine, is a prosthetic group of several acyl carrier proteins including the acyl carrier proteins (ACP) of fatty acid synthases, ACPs of polyketide synthases, the peptidyl carrier proteins (PCP), as well as aryl carrier proteins (ArCP) of nonribosomal peptide synthetases (NRPS). It is also present in formyltetrahydrofolate dehydrogenase.
Lipstatin is a potent, irreversible inhibitor of pancreatic lipase. It is a natural product that was first isolated from the actinobacterium Streptomyces toxytricini.
In molecular biology, Beta-ketoacyl-ACP synthase EC 2.3.1.41, is an enzyme involved in fatty acid synthesis. It typically uses malonyl-CoA as a carbon source to elongate ACP-bound acyl species, resulting in the formation of ACP-bound β-ketoacyl species such as acetoacetyl-ACP.
Thiolases, also known as acetyl-coenzyme A acetyltransferases (ACAT), are enzymes which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway.
The enzyme [acyl-carrier-protein] phosphodiesterase (EC 3.1.4.14) catalyzes the reaction
In enzymology, a β-ketoacyl-[acyl-carrier-protein] synthase III (EC 2.3.1.180) is an enzyme that catalyzes the chemical reaction
Clavams are a class of antibiotics. This antibiotic is derived from Streptomyces clavuligerus NRRL 3585. Clavam is produced to form a new β-lactam antibiotic. This class is divided into the clavulanic acid class and the 5S clavams class. Both groups are the outcomes of the fermentation process produced by Streptomyces spp. Clavulanic acid is a broad-spectrum antibiotic and 5S clavams may have anti-fungal properties. They are similar to penams, but with an oxygen substituted for the sulfur. Thus, they are also known as oxapenams.
Streptogramin B is a subgroup of the streptogramin antibiotics family. These natural products are cyclic hexa- or hepta depsipeptides produced by various members of the genus of bacteria Streptomyces. Many of the members of the streptogramins reported in the literature have the same structure and different names; for example, pristinamycin IA = vernamycin Bα = mikamycin B = osteogrycin B.
Pikromycin was studied by Brokmann and Hekel in 1951 and was the first antibiotic macrolide to be isolated. Pikromycin is synthesized through a type I polyketide synthase system in Streptomyces venezuelae, a species of Gram-positive bacterium in the genus Streptomyces. Pikromycin is derived from narbonolide, a 14-membered ring macrolide. Along with the narbonolide backbone, pikromycin includes a desosamine sugar and a hydroxyl group. Although Pikromycin is not a clinically useful antibiotic, it can be used as a raw material to synthesize antibiotic ketolide compounds such as ertythromycins and new epothilones.
Callystatin A is a polyketide natural product from the leptomycin family of secondary metabolites. It was first isolated in 1997 from the marine sponge Callyspongia truncata which was collected from the Goto Islands in the Nagasaki Prefecture of Japan by the Kobayashi group. Since then its absolute configuration has been elucidated and callystatin A was discovered to have anti-fungal and anti-tumor activities with extreme potency against the human epidermoid carcinoma KB cells (IG50 = 10 pg/ml) and the mouse lymphocytic leukemia Ll210 cells (IG50 = 20 pg/ml).
Germicidins are a groups of natural products arising from Streptomyces species that acts as autoregulatory inhibitor of spore germination. In Streptomyces viriochromogenes, low concentrations inhibit germination of its own arthrospores, and higher concentrations inhibit porcine Na+/K+ -activated ATPase. Inhibitory effects on germination are also observed when germicidin from Streptomyces is applied to Lepidium sativum. Germicidins and other natural products present potential use as pharmaceuticals, and in this case, those with possible antibiotic or antifungal activity.
Kidamycin is an anthracycline antibiotic with anticancer activity. It was first synthesized from a strain of streptomyces bacteria isolated from a soil sample. In clinical trials, Kindamycin showed high effect against gram positive bacteria as well as multiple cancer models including Ehrlich ascites carcinoma, Sarcoma 180, NF-sarcoma, and Yoshida sarcoma.
Ketoacyl synthases (KSs) catalyze the condensation reaction of acyl-CoA or acyl-acyl ACP with malonyl-CoA to form 3-ketoacyl-CoA or with malonyl-ACP to form 3-ketoacyl-ACP. This reaction is a key step in the fatty acid synthesis cycle, as the resulting acyl chain is two carbon atoms longer than before. KSs exist as individual enzymes, as they do in type II fatty acid synthesis and type II polyketide synthesis, or as domains in large multidomain enzymes, such as type I fatty acid synthases (FASs) and polyketide synthases (PKSs). KSs are divided into five families: KS1, KS2, KS3, KS4, and KS5.
Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the atropisomer of abyssomicin C. It is a spirotetronate that belongs to the class of tetronate antibiotics, which includes compounds such as tetronomycin, agglomerin, and chlorothricin. In 2006, the Nicolaou group discovered atrop-abyssomicin C while working on the total synthesis of abyssomicin C. Then in 2007, Süssmuth and co-workers isolated atrop-abyssomicin C from Verrucosispora maris AB-18-032, a marine actinomycete found in sediment of the Japanese sea. They found that atrop-abyssomicin C was the major metabolite produced by this strain, while abyssomicin C was a minor product. The molecule displays antibacterial activity by inhibiting the enzyme PabB, thereby depleting the biosynthesis of p-aminobenzoate.
Hentriacontanonaene is a long-chain polyunsaturated hydrocarbon produced by numerous gamma-proteobacteria primarily from the marine environment. Hentriacontanonaene was originally isolated from bacterial isolates from Antarctic sea ice cores. All isolated bacteria that produced hentriacontanonaene also produced the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Given its polyunsaturated nature it has been proposed that this molecule is produced as part of a response to maintain optimal membrane fluidity.
Borrelidin is an 18-membered polyketide macrolide derived from several Streptomyces species. First discovered in 1949 from Streptomyces rochei, Borrelidin shows antibacterial activity by acting as an inhibitor of threonyl-tRNA synthetase and features a nitrile moiety, a unique functionality in natural products., Borrelidin also exhibits potent angiogenesis inhibition, which was shown in a rat aorta matrix model. Other studies have been performed to show that low concentrations of borrelidin can suppress growth and induce apoptosis in malignant acute lymphoblastic leukemia cells. Borredlidin's antimalarial activity has also been shown in vitro and in vivo.
Butyrolactol A is an organic chemical compound of interest for its potential use as an antifungal antibiotic.
Quinolidomicin A1 is a 60-membered macrocyclic compound isolated from Micromonospora sp. JY16. Quinolidomicins are a class of macrolides that contain a benzoquinone chromophore as well as an immense lactone ring, which far surpasses that in monozanomycin. It is currently the largest identified macrolide of terrestrial origin. It was initially discovered when in a screening for anti-tumor antibiotics, where it was found to be cytotoxic against P388 murine leukemia cells (IC50 8 nM), and has later been found to have strong cytotoxic activity against HT-29, MKN28, K562, and KB.
Pladienolide B is a natural product produced by bacterial strain, Streptomyces platensis MER-11107, which is a gram-positive bacteria isolated from soil in Japan. Pladienolide B is a molecule of interest due to its potential anti-cancer properties. Its anti-cancer mode of action includes binding to the SF3B complex in the U2 snRNP in the human spliceosome.
