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Microbial Metabolism of the Isoprenoid Alkane Pristane (A-Methylglutarate/4,8,12-Trimethyltridecanoate/Fatty Acid Metabolism)

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Microbial Metabolism of the Isoprenoid Alkane Pristane (A-Methylglutarate/4,8,12-Trimethyltridecanoate/Fatty Acid Metabolism) Proc. Nat. Acad. Sci. USA Vol. 68, No. 7, pp. 1552-1554, July 1971 Microbial Metabolism of the Isoprenoid Alkane Pristane (a-methylglutarate/4,8,12-trimethyltridecanoate/fatty acid metabolism) E. J. McKENNA* AND R. E. KALLIO* Department of Microbiology, University of Iowa, Iowa City, Iowa Communicated by N. J. Leonard, May 10, 1971 ABSTRACT The "inert" hydrocarbon pristane (2,6,- (TMTD) acids from Antarctic whale oil through North 10,14-tetramethylpentadecane) can be utilized as the sole Atlantic whale oil to seal oil has suggested to Ackman and source of carbon and energy for growth of a coryneform soil isolate. Identification of the metabolites 4,8,12- Hooper (11) a correlation with change in food intake for trimethyltridecanoic acid and a-methylglutaric acid marine mammals from a primarily zooplankton diet through indicates that two pathways of fatty acid metabolism a partial fish diet to an exclusive fish diet. More recently, operate in this bacterial strain. Blumer et al. (12) have isolated three phytol-derived olefinic The widespread use of pristane as a biological marker (the 2,10- and 5,10-diene and the 2,6,10-triene appears to be predicated on its structural similarity to hyrocarbons phytol and its apparent stability, which may be only a analogs of pristane) from marine zooplankton and fishes. reflection of the inability of microorganisms to carry out Since these olefins are not present in ancient sediments and its anaerobic destruction. petroleum, they are considered to be valuable markers for the distinction between marine oil pollution and hydrocarbons Isoprenoid hydrocarbons are ubiquitous natural products. derived from organisms. Pristane (2,6,10,14-tetramethylpentadecane), presumably Despite pristane's "inertness", we had found in a growth derived from the phytol moiety of chlorophyll present in survey of bacteria known to utilize n-alkanes that under photosynthetic organisms, has been detected in bacteria, proper conditions pristane is readily utilized by a variety of algae (1), and higher plants (2); traces of pristane also have organisms (13). In addition to the mycobacteria, nocardiae, been reported in human sebaceous lipids (3), in various tissues and one moraxella strain tested in the growth study, several of the human and cow, in rat liver, and in wool wax (2). soil isolates also utilized pristane as a sole carbon and energy Marine sources of pristane include zooplankton, lobster, fish, source for growth. One stain, tentatively identified as a species sharks, sperm whale (4), and recent sediments (5). Fossil of Corynebacterium and designated RTMP-S, was chosen for fuels such as coal and petroleum contain this isoprenoid al- further study because of its consistently profuse growth on kane, as do ancient sediments (6). The stable structure persists pristane. even in Precambrian rocks (6) and perhaps is indigenous to The soil isolate was grown in a mineral-salts medium at extraterrestrial meteorites (1). the expense of 0.2% pristane in shake culture for 80 hr, the Pristane's relative inertness accounts for its usefulness as a time of maximum metabolite accumulation. Culture fluids biological marker. The coexistence of microfossils with pris- (30 liters) were concentrated under reduced pressure and the tane and phytane (2,6,10,14-tetramethylhexadecane) in crude concentrate (1 g), when fractionated by column chro- Precambrian rocks is significant to the paleobotanist investi- matography on silicic acid, yielded a minor fraction, eluted gating the antiquity of life on earth (7). In detection of these with hexane-diethyl ether-acetic acid (90: 10: 1, Solvent 1), markers, geologists have a new tool for determining the en- and a major fraction, which was eluted when the proportion vironment of the earth in past geological epochs (8). Mein- of ether was increased (hexane-diethyl ether-acetic acid, schein et al. (9) have employed long-chain alkanes (C,5-C3o) 60:40:1, Solvent 2). The major fraction crystallized readily as biological markers in exobiological research. Neither pris- from benzene. Recrystallization from hexane-ether and final tane nor any other alkane in the indicated molecular-weight purification by sublimation yielded 155 mg of colorless crys- range was found at a concentration exceeding one part per tals, mp (uncor) 74.5°C; elemental analysis: C, 49.38; H, 6.75 billion by weight in a 50-g sample of lunar fines. The pristane (C6H1004 requires C, 49.32; H, 6.85%); neutralization equiva- content of the digestive tract of the basking shark is con- lent, 72.9. Gas-liquid chromatography on Apiezon L (1800C) sidered to be indicative of food sources and feeding grounds of and on LAC-2-R 446 (1150C) gave equivalent chain lengths of the shark; thus the marine biologist finds hydrocarbon (ECL) of 5.3 and 5.5, respectively, while thin-layer chroma- analysis potentially useful in studies of the movement of tography on silica gel G (Solvent 2) revealed an Rr (relative marine animals (10). The gradation in proportions of phytanic to palmitic acid) of 0.14. Both cochromatography and mixed (3,7,11,15-tetramethylhexadecanoic), pristanic (2,6,10,14- melting points of this fraction and authentic a-methylglu- tetramethylpentadecanoic), and 4,8,12-trimethyltridecanoic taric acid were identical to that of the reference compound alone; infrared and nuclear magnetic resonance spectra of the Abbreviations: ECL, equivalent chain length; TMTD, 4,8,12- two compounds further confirmed the identity (13). trimethyltridecanoate. The minor fraction (19 mg) exhibited an Rf value of 0.96 * Present address: Department of Microbiology, University of relative to palmitic acid upon thin-layer chromatography on Illinois, Urbana, Ill. 61801. silicic acid in Solvent 1, and this monocarboxylic acid fraction 1552 Downloaded by guest on September 23, 2021 Proc. Nat. Acad. Sci. USA 68 (1971) Microbial Metabolism of Pristane 1553 could be separated into some fifteen components (as methyl Ivv esters) by gas-liquid chromatography on either a polar (LAC- C H3 C H3 CH3 C H30 -C1- (C H2)20 CH3-0-C-lCH2)2, -CHtCH0)3-CH,T(CH2)3I-"2-tH3 446 at 190°C) or a L at A 12 nonpolar (Apiezon 240'C) phase. 80 O 4 plot of equivalent chain length (ECL) against total number of 87 ns5 157 185 227 carbon atoms in the acid of the ester deter- moiety methyl U) mined mass revealed the of z 60- by spectrometry presence long- w as chain saturated and monounsaturated normal acids, well z as saturated acids with from one to four branches (13). 74 1 ," 115 / 157 185 227 methyl w 40 _- One major component in this fraction '(Cut A) exhibited an p ECL of 14.3 on Apiezon L, similar to that for TMTD found I M-31 -i 12 /I8 Hansen of and Blumer and Cooper w by (14) (ECL 14.4) (15) ct 201 (ECL of 14.35) on the same nonpolar phase. The same ECL i~11'A'~~~~~~M5/, 2,e/,,,,M-29 of 14.3 was obtained on a polar LAC-2-R 446 (diethylene glycol-pentaerythritol adipate) column, which corresponded 0 well with Sano's (16) value of 14.3 on polyester and the ECL of 20 60 lo 40 180 220 260 300 Ackman et al. (17) (14.18 on capillary butanediol succinate m/e columns) for this acid. The mass spectrum of cut A (Fig. 1) FIG. 1. Mass spectrum of gas-liquid chromatographic cut A corresponds closely with that of the methyl ester of TMTD from the methyl esters of the monocarboxylic acid fraction. The reported by several workers (14, 16, 18-20). spectrum, obtained by P. A. Wadsworth and D. P. -Stevenson Neither a-methylglutaric acid nor TMTD was present in through the courtesy of the Shell Development Company, 80-hr culture fluids of cells grown on n-pentadecane. Similarly, Emeryville, Calif., was given by a CEC 21-103 mass spectrometer no growth on pristane occurred anaerobically in the presence with a 250°C inlet reservoir and 75-V ion source. of nitrate. The above acids are thought to have arisen from pristane in the following manner (Fig. 2): pristane is initially oxidized a-Methylglutaric acid could be formed via cw-oxidation of a to pristanic acid, which can then give rise to TMTD by B long-chain monocarboxylic acid, first reported in bacteria oxidation and cleavage of the coenzyme A thioester of pris- by Kester and Foster (24). Jones (25) has shown thaft, in a tanic acid. Two- and three-carbon fragments formed alter- medium containing glucose, the yeast Torulopsis gropengiesseri nately upon successive ,B-oxidation, and cleavage steps of the can convert pristane into glycolipids containing 2,6,10,14- original pristanic acid (19, 21) could then participate in tetramethylpentadecane-1-ol, 2,6,10,14-tetramethylpentade- synthesis of cell components. Mammals such as mice fed cane-1,15-diol, and traces of 15-hydroxy-2,6,10,14-tetra- phytol or phytanic acid (19) and rats fed phytanic acid (22) methylpentadecanoic acid. Although cw-oxidation could con- accumulate small but significant amounts of TMTD in the ceivably occur at any one of several stages of the ,B-oxidative body (less than the amount of phytanic acid but approxi- degradation of pristanic, acid, chromatographic data on a mately equal to the amount of pristanic acid accumulated). minor polar fraction from silica gel chromatography indicated Sheep perinephric fat contains traces of TMTD, which are that a long-chain dicarboxylic acid was formed during pristane postulated to have arisen by the action of rumen bacteria on oxidation (13). Since strain RTMP-S did not show an ap- phytol (14). Presumably, the TMTD found in marine life preciable growth response to a-methylglutarate but grew (fishes and mammals) (11, 17, 18), recent marine sediments well on methylmalonate, the step from ca-methylglutarate (15), and the shale (23) and kerogen matrix (20) of the Green to methylmalonate is apparently rate-limiting.
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