derived from seawater has shown that a teria(>80 percent of all our microbial drug discovery.When the sheer immen. truly amazing compleity of microbial antibiotics are produced by this ass sity of the ocean bottom is considered life exists in the sea (Venter et al.,2004). of bacteria)were found there.The best (70 percent of Earth's surface),it is not These studies have further shown that example is the recently discovered and difficult to conceive of the importance microbial diversity varies by 8 percent widely distributed marine actinomy- of these resources in contributing to the between samples collected only 100 miles cete genus,Salinispora,which produces badly needed antibiotics for the next (161km)apart. a diversity of no molecules such as millennium (Figure9). Clearly,new genomics tools are great- salinosporamide A,a potent cancer cell As time passes,marine scientists are ly expanding our understanding of mi- growth inhibitor scheduled for clinical continually illustrating the important crobial diversity of the open ocean.One evaluation in 2006 (Figure8).At least roles symbiotic bacteria play in the bio of our greatest resources now appears to 13 new groups (likely to be new genera) synthesis of invertebrate-derived drug be deep ocean sediments.Althe ugh sedi- of actino ia have een dis. candidates.That microbes are found ments have been known for decades to covered in the last three years (Jensen in symbiotic relationships with inver harbor over 10 microbial cells per cubic et al.,2005;Stach and Bull,2005),sug- tebrates is almost the rule in marine centimeter,it was just recently that the gesting that these chemically rich micro- systems,but it has taken more thar medically significant actinomycete bac organisms will be a major resource for 30 years to begin to define their roles.A recent example is the discovery that the manzamine alkaloids,originally isolated from diverse sponges,are produced by an actinomycete bacterium of the genus Micromonospora,isolated directly from the invertebrate host (Figure 10).This is ete,Salinispora tropica,the of great importance,as the manzamines source of the potent protea are potent anti-malarial agents currently A(shown).Salinosporamide A in preclinical trials(Rao et) vill enter clinical trials in mid It is also easy to predict that the role of combinatorial gene biosynthesiswill increase as new sources for novel mol ecules are"manufactured"by cleverly combining and eliminating genes from whole biosynthetic gene clusters.It has also been shown that complex DNA can be extracted from environmental samples and expressed in host bacteria to gener- ate molecules not seen before(Brady and Clardy,2000;Brady et al.,2001;Clardy. 2005).Although this is reality in 2006. these studies are pioneering,and few complex pathways have been cloned. ent antibacterial activity agains Although not yet routine,these new bio technologies applied to the biosyntheti- rusand vancomycin-re cally complex life in the sea are likely to Enterococcus faecium. create immense chemical diversity. 118 Occanography I Vol 19,No.2.June 2006118 Oceanography Vol. 19, No. 2, June 2006 drug discovery. When the sheer immen￾sity of the ocean bottom is considered (70 percent of Earth’s surface), it is not diffi cult to conceive of the importance of these resources in contributing to the badly needed antibiotics for the next millennium (Figure 9). As time passes, marine scientists are continually illustrating the important roles symbiotic bacteria play in the bio￾synthesis of invertebrate-derived drug candidates. That microbes are found in symbiotic relationships with inver￾tebrates is almost the rule in marine systems, but it has taken more than 30 years to begin to defi ne their roles. A recent example is the discovery that the manzamine alkaloids, originally isolated from diverse sponges, are produced by an actinomycete bacterium of the genus Micromonospora, isolated directly from the invertebrate host (Figure 10). This is of great importance, as the manzamines are potent anti-malarial agents currently in preclinical trials (Rao et al., 2004). It is also easy to predict that the role of combinatorial gene biosynthesis will increase as new sources for novel mol￾ecules are “manufactured” by cleverly combining and eliminating genes from whole biosynthetic gene clusters. It has also been shown that complex DNA can be extracted from environmental samples and expressed in host bacteria to gener￾ate molecules not seen before (Brady and Clardy, 2000; Brady et al., 2001; Clardy, 2005). Although this is reality in 2006, these studies are pioneering, and few complex pathways have been cloned. Although not yet routine, these new bio￾technologies applied to the biosyntheti￾cally complex life in the sea are likely to create immense chemical diversity. derived from seawater has shown that a truly amazing complexity of microbial life exists in the sea (Venter et al., 2004). These studies have further shown that microbial diversity varies by 80 percent between samples collected only 100 miles (161 km) apart. Clearly, new genomics tools are great￾ly expanding our understanding of mi￾crobial diversity of the open ocean. One of our greatest resources now appears to be deep ocean sediments. Although sedi￾ments have been known for decades to harbor over 109 microbial cells per cubic centimeter, it was just recently that the medically signifi cant actinomycete bac￾teria (> 80 percent of all our microbial antibiotics are produced by this class of bacteria) were found there. The best example is the recently discovered and widely distributed marine actinomy￾cete genus, Salinispora, which produces a diversity of novel molecules such as salinosporamide A, a potent cancer cell growth inhibitor scheduled for clinical evaluation in 2006 (Figure 8). At least 13 new groups (likely to be new genera) of actinomycete bacteria have been dis￾covered in the last three years (Jensen et al., 2005; Stach and Bull, 2005), sug￾gesting that these chemically rich micro￾organisms will be a major resource for Figure 8. Close-up photograph of the new marine actinomy￾cete, Salinispora tropica, the source of the potent protea￾some inhibitor salinosporamide A (shown). Salinosporamide A will enter clinical trials in mid 2006 with the primary target being multiple melanoma. Figure 9. Th e new actinomycete genus “Marinispora,” produces novel polyene-polyols with po￾tent antibacterial activity against drug resistant pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium