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Collections of the marine cyanobacterium Lyngbya bouillonii from shallow patch reefs in Apra Harbor, Guam, afforded three hitherto undescribed analogues of the glycosidic macrolide lyngbyaloside, namely, 2-epi-lyngbyaloside (1) and the regioisomeric 18E- and 18Z-lyngbyalosides C (2 and 3). Concurrently we discovered two new analogues of the cytoskeletal actin-disrupting lyngbyabellins, 27-deoxylyngbyabellin A (4) and lyngbyabellin J (5), a novel macrolide of the laingolide family, laingolide B (6), and a linear modified peptide, lyngbyapeptin D (7), along with known lyngbyabellins A and B, lyngbyapeptin A, and lyngbyaloside. The structures of 1-7 were elucidated by a combination of NMR spectroscopic and mass spectrometric analysis. Compounds 1-6 were either brominated (1-3) or chlorinated (4-6), consistent with halogenation being a hallmark of many marine natural products. All extracts derived from these L. bouillonii collections were highly cytotoxic due to the presence of apratoxin A or apratoxin C. Compounds 1-5 showed weak to moderate cytotoxicity to HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells.

Field collections of the red macroalgae Ochtodes secundiramea and Portieria hornemannii exhibit site-to-site variations in halogenated monoterpene (HMT) content. In contrast, microplantlets of O. secundiramea and P. hornemannii established through cell and tissue culture techniques had remarkably similar HMT profiles when cultivated in a photobioreactor under identical, controlled conditions. Both algae shared Apakaochtodene B (6) as the only cyclic HMT, 10E-bromomyrcene (3) and 10E-bromo-3-chloro-alpha-myrcene (4) as the dominant acyclic HMTs, and myrcene (1) as their common precursor. Furthermore, HMT yields were comparable between organisms (0.9-1.3 micromol/g dry mass of 6; 3.4-4.4 micromol/g of 3). P. hornemannii microplantlets also contained 7-chloromyrcene (9) as the dominant compound (37-73 micromol/g), suggesting additional chlorination capacity. Proposed pathways for HMT biosynthesis shared by P. hornemannii and O. secundiramea microplantlets possessed two common manifolds: (a) bromonium ion (Br(+))-catalyzed cyclization of 1, followed by chlorination to yield 6; (b) Markovnikov addition of Br(+) at Delta(6,10) of 1 to yield 3 with a marked selectivity (>50:1) for the E isomer, followed by chlorination of 3 to 4. This study demonstrated that bioreactor tissue culture is a new venue for bioprospecting and production of natural compounds from marine macroalgae under a controlled environment.