Psymberin, also known as irciniastatin A, is a

cytotoxin Cytotoxicity is the quality of being toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium ...

derived from

sea sponge Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a basal clade and a sister taxon of the diploblasts. They are sessile filter feeders that are bound to the seabed, and are o ...

s. It was discovered by two independent research groups, one led by Dr. Phil Crews and one led by Dr. Jean Schmidt, in 2004. Psymberin was found to be highly bioactive as it showed

LC50 In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a given substance. The value of LD50 for a substance is the dose requir ...

s at nanomolar concentrations against various types of

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

Biosynthesis

The biosynthesis of psymberin became of interest when it was found to have a very similar structure to

pederin Pederin is a vesicant toxic amide with two tetrahydropyran rings, found in the haemolymph of the beetle genus ''Paederus'', including the Nairobi fly, belonging to the family Staphylinidae. It was first characterized by processing 25 million field ...

, a natural product derived from the beetle genus ''

Paederus ''Paederus'' is a genus of small beetles of the Family (biology), family Staphylinidae ("rove beetles"). With 622 valid species assigned by 1987 to the subtribe Paederina (''Paederus'' and its close allies), and with all but 148 within ''Paederu ...

''. This led researchers to investigate the genes of the organism that code for the respective natural product. A trans-AT

polyketide synthase Polyketide synthases (PKSs) are a family of multi- domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share ...

cluster, designated as the ''Psy'' cluster, contained two large groups of

genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

coding for two PKSs. The smaller gene group, ''psyA'', encoded a PKS with three modules, while the larger ''psyD'' encoded a ten module PKS. This ten module PsyD

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

is, to date, the protein with the highest reported number of PKS modules. Large portions of the gene cluster ''psyD'' have very close counterparts in the pederin gene clusters. This indicates that psymberin and pederin are both structurally and biosynthetically related. The figure below shows the proposed biosynthesis of psymberin based on analysis of the gene clusters.

Roman numerals Roman numerals are a numeral system that originated in ancient Rome and remained the usual way of writing numbers throughout Europe well into the Late Middle Ages. Numbers are written with combinations of letters from the Latin alphabet, eac ...

represent which

clade In biology, a clade (), also known as a Monophyly, monophyletic group or natural group, is a group of organisms that is composed of a common ancestor and all of its descendants. Clades are the fundamental unit of cladistics, a modern approach t ...

each Ketosynthase domain belongs. The domains outlined in red represent carrier proteins. The following abbreviations correspond to the figure below: GNAT, GCN5-related N-acetyltransferase; CR, crotonase; KR, ketoreductase; KS⁰, non-elongating ketoreductase; OMT, O-methyltranfserase; C, nonribosomal peptide synthetase (NRPS)

condensation domain In molecular biology, the condensation domain is a protein domain found in many multi-domain enzymes which synthesise peptide antibiotics. This domain catalyses a condensation reaction to form peptide bonds in non-ribosomal peptide biosynthesis. I ...

; A, NRPS adenylation domain; MT, Methyltransferase; DH, deydratase; TE, Thioesterase; ?, unknown.

References

External links

* {{MeshName, Psymberin Sponge toxins

Biosynthesis

See also

References

External links