Pseudopterosin Biosynthesis: Unravelling a Decades Old Problem in Animal Specialized Metabolism.

Soft corals are prolific producers of terpenoids, such as pseudopterosins. The exact biosynthetic pathway of these anti-inflammatory diterpene glycosides has eluded the scientific community for decades. Using a forward genetic approach, we have identified, cloned, and expressed the key genes involved in pseudopterosin biosynthesis.

Brewing coral terpenes-A yeast based approach to soft coral terpene cyclases.

Coral terpenes are important molecules with numerous applications. Here, we describe a robust and simple method to produce coral terpene scaffolds at scale. As an example of the approach, here we discover, express, and characterize further klysimplexin R synthases, expanding the known enzymology of soft coral terpene cyclases.

Enantioselective Synthesis of (+)-Providencin and Its Unexpected Regioisomer via a Biomimetic Norrish-Yang Cyclization from (-)-Bipinnatin E.

A biomimetic semisynthesis of the diterpenoid (+)-providencin () and the unexpected novel C14 regioisomer was achieved by photoirradiation of the proposed biosynthetic cembranoid precursor (-)-bipinnatin E (). The absolute configuration assignments of and by correlation were established by X-ray analysis. A combination of NOESY data and photochemical reaction results revealed that both C2 and C14 positions of the macrocycle (-)- are suitable for hydrogen abstraction, thus affording an explanation to the mixture of cyclobutane photoproduct isomers obtained by a Norrish-Yang cyclization.

Biomimetic Approach to Diverse Coral Diterpenes from a Biosynthetic Scaffold.

Thousands of coral terpenes originate from simple scaffolds that undergo oxidative tailoring. While corals are excellent sources of drug leads, the challenge of supplying structurally complex drug leads from marine organisms has sometimes slowed their development. Making this even more challenging, in comparison to other organisms, such as plants and microbes, for which the terpene literature is substantial, very little is known about how the unique coral terpenes are biosynthesized and elaborated in nature.

AgeMTPT, a Catalyst for Peptide N-Terminal Modification.

A key goal of synthetic biology is to enable designed modification of peptides and proteins, both in vivo and in vitro. N- and C-Terminal modification enzymes are crucial in this regard, but there are a few enzymatic options to protect peptide termini. AgeMTPT protects the N-terminus of short peptides with isoprene and the C-terminus as a methyl ester, but its substrate scope is unknown, limiting its application.

Ancient defensive terpene biosynthetic gene clusters in the soft corals.

Diterpenes are major defensive small molecules that enable soft corals to survive without a tough exterior skeleton, and, until now, their biosynthetic origin has remained intractable. Furthermore, biomedical application of these molecules has been hampered by lack of supply. Here, we identify and characterize coral-encoded terpene cyclase genes that produce the eunicellane precursor of eleutherobin and cembrene, representative precursors for the >2,500 terpenes found in octocorals.

Role of Macrocyclic Conformational Steering in a Kinetic Route toward Bielschowskysin.

Macrocyclic furanobutenolide-derived cembranoids (FBCs) are the biosynthetic precursors to a wide variety of highly congested and oxygenated polycyclic (nor)diterpenes (e.g. plumarellide, verrillin, and bielschowskysin).