Tambjamines are a group of

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical sy ...

s that are structurally related to the

prodiginine The prodiginines are a family of red tripyrrole dyestuffs produced by Gammaproteobacteria (e.g. ''Serratia marcescens'') as well as some Actinomycetota (e.g. ''Streptomyces coelicolor''). The group is named after prodigiosin (prodiginine) and is b ...

s. They are

enamine An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates. : The word "enamine" is derived from the affix ''en''-, used as the suffix of alkene, and the ...

derivatives of 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC).

Chemical structure

Tambjamines are composed of two

pyrrole Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4 H4 NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., ''N''-met ...

rings with an enamine moiety at C-5 and a

methoxy group In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula . On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position a ...

at C-4: the majority have short

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloal ...

chains connected to the enamine nitrogen. This group of

alkaloid Alkaloids are a class of basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Th ...

s have been isolated from marine invertebrates and bacteria (both marine and terrestrial). Tambjamine A.png, Tambjamine A Tambjamine B.png, Tambjamine B Tambjamine C.png, Tambjamine C Tambjamine E.png, Tambjamine E Tambjamine K.png, Tambjamine K

Marine sources and ecological roles

The large

nudibranch Nudibranchs () are a group of soft-bodied marine gastropod molluscs which shed their shells after their larval stage. They are noted for their often extraordinary colours and striking forms, and they have been given colourful nicknames to mat ...

'' Roboastra tigris'' is a known predator of ''

Tambja eliora ''Tambja eliora'' is a species of sea slug, a dorid nudibranch, a marine gastropod mollusk in the family Polyceridae The Polyceridae are a taxonomic family of sea slugs, dorid nudibranchs, marine gastropod mollusks within the superfamily ...

'' and ''

Tambja abdere ''Tambja abdere'' is a species of sea slug, a dorid nudibranch, a marine gastropod mollusk in the family Polyceridae The Polyceridae are a taxonomic family of sea slugs, dorid nudibranchs, marine gastropod mollusks within the superfamily ...

'', two species of smaller nudibranchs. The chemical extracts of all three nudibranch species contain tambjamines, which were traced to ''Sessibugula translucens'', a food source of the two prey species. It is hypothesized that tambjamines are a chemical defence mechanism of the bryozoan against feeding by the spotted kelpfish ''

Gibbonsia elegans ''Gibbonsia elegans'', the spotted kelpfish, is a species of clinid native to subtropical waters of the Pacific Ocean from central California, U.S. to southern Baja California, Mexico. It prefers subtidal rocky habitats with seaweed down to a d ...

''.

Production

Biosynthesis

The biosynthetic gene cluster responsible for tambjamine production was identified in 2007 using functional genomic analysis of a ''

Pseudoalteromonas tunicata ''Pseudoalteromonas tunicata'' is a marine bacterium isolated from the tunicate ''Ciona intestinalis ''Ciona intestinalis'' (sometimes known by the common name of vase tunicate) is an ascidian (sea squirt), a tunicate with very soft tunic. It ...

'' strain. The Tam cluster consists of 19 proteins, 12 of which were found to be highly similar to proteins in the Red and Pig pathways from prodigiosin biosynthesis, based on sequence data. The biosynthesis of tambjamine YP1 first involves the incorporation of proline, malonyl Co-A, and serine to form 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC). AfaA is hypothesized to activate long-chain fatty acids while the predicted

dehydrogenase A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as ...

, TamT, introduces a double bond into a fatty acyl side chain. TamH then carries out the reduction of the CoA-ester to form an aldehyde intermediate, followed by transamination.

Condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...

of the dodec-3-en-1-amine product of this reaction and MBC by TamQ, results in the tambjamine YP1 (compound 21 in Figure 1).

Laboratory

The aldehyde MBC was first prepared by

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

when the structure of prodigiosin was being investigated. It has subsequently been synthesised by other methods and used to make tambjamines and related natural products.

References