Sporolides A and

In the attempt to unravel the biosynthetic origin of sporolides, and considering that these compounds are composed of a chlorinated cyclopenta[a]indene ring and a cyclohexenone moiety, it was hypothesized that the former fragment could be nonenzymatically derived from an unstable nine-membered enediyne precursor by the nucleophilic addition of chloride. Support to this suggestion came from sequence analysis of S. tropica CNB-440 genome, which led to the identification of two biosynthetic loci encoding enediyne PKSs. Analysis of the respective 

THREE-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

Subsequently, the organization of the 60-kb biosynthetic gene cluster of sporolides was reported. Putative assignments include spoE, E2-E11, and spoF in the biosynthesis of the enediyne core, spoTl-TlO in the construction and attachment of the cyclohexenone precursor, 6 genes involved in regulation, transport, and resistance, and 19 of unknown or unassigned function [472]. 

Tsuchida T, Sawa R, Takahashi Y, linuma H, Sawa T, Naganawa H, Takeuchi T J. Antibiot. 1995,48, 1148-1152. 

Tabares P, Degel B, Schaschke N, Hentschel U, Schirmeister T, Pharmacogn. Res. 2012,4, 63-66. 

---

Buchanan GO, Williams PG, Feling RH, Kauffman CA, Jensen PR, Fenical W (2005) Sporolides A and B Structurally Unprecedented Halogenated Macrolides from the Marine Actinomycete Salinispora tropica. Org Lett 7 2731... 

Sporolides A and B were isolated in 2005 from a fermentation broth of a strain of the marine actinomycete Salinispora tropica. The structures 377 and 378 and the absolute stereochemistries for sporolide A and sporolide B were elucidated using a combination of NMR spectroscopy and X-ray crystallography. Unformnately, the sporolides, tested for antitumor and antibacterial activity, were inactive (Figure 3.130) [470]. 

Figure 3.131 Proposed biosynthesis of the precursor of the cyclohexenone moiety of sporolides A and B.

Figure 1. Naturally occurring enediynes and natural products for which enediynes have been proposed as biosynthetic intermediates, (a) The 10-memberedfamily includes calicheamicin, dynemicin, esperamicin, shishijimicin, namenamicin, and uncialamycin. (b) The 9-membered enediynes include neocarzinostatin (NCS), C-1027, maduropeptin, kedarcidin, andN1999A2. (c) Sporolides A and B and cyanosporasides A and B are all hypothesized to originate from enediyne precursors (bracketed) based on the presence of the enediyne polyketide synthase (PKSE) in the Salinaspora genome of each producing organism.

Recent application of PKSE data sets and the noted PCR-based strategy has revealed that the biosynthetic gene cluster for sporolides A and B contains two loci encoding PKSEs 13). Produced by Salinispora tropica, sporolides A and B do not contain enediynes per se (Figure Ic). Rather, each substance contains a tricyclic motif that is proposed to originate biosynthetically from a transient... 

Buchanan, G,0 Williams, P,G Feling, R.H., Kauffman, C.A, Jensen, P.R., and Fenical, W, (2005) Sporolides A and B Structurally unprecedented halogenated macrolides from the marine actinomycete Salinispora tropica. Org. Lett., 7, 2731-2734. 

---