BIOSYNTHESIS OF THE MODIFIED PEPTIDE ANTIBIOTIC THIOSTREPTON IN STREPTOMYCES-AZUREUS AND STREPTOMYCES-LAURENTII

被引:96
作者
MOCEK, U
ZENG, ZP
OHAGAN, D
ZHOU, P
FAN, LDG
BEALE, JM
FLOSS, HG
机构
[1] UNIV WASHINGTON,DEPT CHEM,SEATTLE,WA 98195
[2] OHIO STATE UNIV,DEPT CHEM,COLUMBUS,OH 43210
关键词
D O I
10.1021/ja00071a009
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The biosynthesis of the thiopeptide antibiotic thiostrepton (1) has been investigated by administration of isotopically labeled precursors to cultures of Streptomyces azureus and Streptomyces laurentii. The amino acid origin of all the components of the antibiotic was demonstrated. Experiments with (S)-[1,2-C-13(2)]- and (S)-[2,3-C-13(2)]serine showed intact incorporation of serine into the thiazoline and thiazole rings as well as the dehydroalanine, alanine, and tetrahydropyridine moieties. (S)-[3-C-13,H-2(2)]Serine and (2S,3S)-[3-C-13,H-2(1)]serine were used to elucidate the stereochemistry of the various transformations of serine. The quinaldic acid moiety arises from (S)-tryptophan and the methyl group of methionine; using methionine carrying a chiral methyl group, it was shown that this methylation proceeds with retention of configuration of the methyl group. Efficient incorporation of (R,S)-2-methyl-[3'-C-13]tryptophan proved that the methylation is the first step in the sequence, followed by an intramolecular ring expansion reaction in which the bond between N1 and C2 of the indole ring is cleaved and a new bond is formed between this nitrogen and the side chain alpha carbon. This quinaldic acid moiety is elaborated separately and then attached to the peptide backbone. Possible mechanisms of some of the key reactions and the mode of assembly of the modified peptide structure are discussed.
引用
收藏
页码:7992 / 8001
页数:10
相关论文
共 102 条
  • [1] STRUCTURE OF THIOSTREPTON
    ANDERSON, B
    CROWFOOT.D
    VISWAMIT.MA
    [J]. NATURE, 1970, 225 (5229) : 233 - &
  • [2] Arigoni D., 1978, CIBA FDN S, P243
  • [3] BANERJEE S, 1988, J BIOL CHEM, V263, P9508
  • [4] DELTA-(L-ALPHA-AMINOADIPYL)-L-CYSTEINYL-D-VALINE SYNTHETASE (ACV SYNTHETASE) - A MULTIFUNCTIONAL ENZYME WITH BROAD SUBSTRATE-SPECIFICITY FOR THE SYNTHESIS OF PENICILLIN AND CEPHALOSPORIN PRECURSORS
    BANKO, G
    DEMAIN, AL
    WOLFE, S
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (09) : 2858 - 2860
  • [5] NATURAL ABUNDANCE C-13-C-13 COUPLING OBSERVED VIA DOUBLE-QUANTUM COHERENCE
    BAX, A
    FREEMAN, R
    KEMPSELL, SP
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (14) : 4849 - 4851
  • [6] NUCLEOTIDE-SEQUENCES ENCODING AND PROMOTING EXPRESSION OF 3 ANTIBIOTIC-RESISTANCE GENES INDIGENOUS TO STREPTOMYCES
    BIBB, MJ
    BIBB, MJ
    WARD, JM
    COHEN, SN
    [J]. MOLECULAR & GENERAL GENETICS, 1985, 199 (01): : 26 - 36
  • [7] BILLICH A, 1987, J BIOL CHEM, V262, P17258
  • [8] DEGRADATION OF THIOSTREPTON - STRUCTURE OF THIOSTREPTINE
    BODANSZKY, M
    ALICINO, J
    WILLIAMS, NJ
    BIRKHIMER, CA
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1962, 84 (10) : 2003 - &
  • [9] THIOSTREPTON - DEGRADATION PRODUCTS + STRUCTURAL FEATURES
    BODANSZKY, M
    BIRKHIMER, CA
    FRIED, J
    ALICINO, J
    WILLIAMS, NJ
    KEELER, BT
    COHEN, AI
    SHEEHAN, JT
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1964, 86 (12) : 2478 - &
  • [10] Degradation of thiostrepton. Thiostreptoic acid
    Bodanszky, Miklos
    Sheehan, John Timothy
    Fried, Josef
    Williams, Nina J.
    Birkhimer, Carolyn A.
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1960, 82 (17) : 4747 - 4748