title: Coupled Biosynthesis of Volatiles and Salinosporamide A in Salinispora tropica.
abstract: Terrestrial bacteria, especially actinomycetes, are known to be prolific producers of volatile compounds. We show here that bacteria from ocean sediments can also release complex bouquets of volatiles. The actinomycete Salinispora tropica produces cyclohexenyl compounds not previously known in nature, such as methyl cyclohex-2-ene-1-carboxylate (9), methyl 2-(cyclohex-2-en-1-yl)acetate (10), methyl (E/Z)-2-(cyclohex-2-en-1-ylidene)acetate (11/12), and related alcohols 8 and 13. These compounds were identified by GC/MS and confirmed by synthesis. In addition, rare spiroacetals, aromatic compounds, short-chain acids and esters, alcohols, and various cyclic compounds were produced by the bacteria. The biosynthesis of the cyclohexenyl compounds is closely coupled to that of cyclohexenylalanine (4), a building block of salinosporamide A, a proteasome inhibitor produced by S. tropica. Analysis of S. tropica strains that harbor knockouts of the salinosporamide biosynthetic genes salX and salD, coupled with feeding experiments, revealed that 3-(cyclohex-2-en-1-yl)-2-oxopropanoic acid (60) and 3-(cyclohex-2-en-1-ylidene)-2-oxopropanoic acid (isomers 61 and 62) are important intermediates in the biosynthesis of salinosporamide A, 4, and 8-13.
authors.affiliation: Institute of Organic Chemistry, Technische Universität Braunschweig, Hagenring 30, 38106, Braunschweig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Groenhagen
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Ana Ligia
authors.initials: AL
authors.lastname: Leandrini De Oliveira
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Elisha
authors.initials: E
authors.lastname: Fielding
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Bradley S
authors.identifier: 0000-0002-4652-1253
authors.initials: BS
authors.lastname: Moore
authors.affiliation: Institute of Organic Chemistry, Technische Universität Braunschweig, Hagenring 30, 38106, Braunschweig, Germany. stefan.schulz@tu-bs.de.
authors.forename: Stefan
authors.identifier: 0000-0002-4810-324X
authors.initials: S
authors.lastname: Schulz
mesh_terms: D039903:Actinobacteria / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*; D055549:Volatile Organic Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007783:Lactones; D011758:Pyrroles; D055549:Volatile Organic Compounds; C475865:marizomib
keywords: actinomycetes; amino acids; marine bacteria; natural products; spiroacetals