臺灣三種海洋細菌之生物活性成分研究
以三種不同培養基篩選出 143 株海洋細菌株,經醱酵培養後,萃取液初步以抑制一氧化
氮合成酶 (NOS) 的活性與利用 Phenylephrine 誘發大鼠 (Sprague-Dawley Rat) 胸主動
脈收縮活性平台進行篩選出具有抑制血管收縮的菌株。結果自 143 株海洋菌株萃取液中
發現二株對於 RAW 264.7 細胞具有細胞毒性,分別為 Streptomyces sp. (#HYC21) 和
Pseudoalteromonas sp. (#HYC13) ,另一株 Pseudomonas aeruginosa (#M1B) 則具有抑制
血管收縮的活性,後續針對這三株具有生物活性的菌株以 PPY 、 PY 和 PYG 培養基分
批擴大培養,進行一系列的分析、分離、純化與構造解析,計分離、決定出二十一個化
合物,包括:二個環肽類抗生素 (cyclic peptide antibiotics) 的 actinomycin X2 (1) 、 acti
nomycin D (2) ;二個多溴酚類抗生素 (polybrominated phenolic antibiotics) 的 pentabro
mopseudilin (8) 和 3,3′,5,5′-tetrabromo-2,2′-biphenyldiol (9) ;三個膽酸及其類似物 (choli
c acid and its analogs) 的 cholic acid (10) 、 deoxycholic acid (11) 、 glycocholic acid (12)
;五個喹啉生物鹼 (quinoline alkaloid) 分別為 2- heptylquinol-4-one (13) 、 2-heptyl-3-h
ydroxyquinolin-4(1H)-one (14) 、 2-(1′E-nonenyl)quinol-4-one (15) 、 2-nonylquinol-4-one
(16) 、 3-heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione (17) ;二個酚類化合物
(phenolics) 的 2-(2-hydroxyphenyl)-2-thiazoline-4-methanol (18) 、 4,4′-isopropylidenebisp
henol (19) ;一個吩嗪生物鹼 (phenazine alkaloid) phenazine-1-carboxamide (21) 及五個
環化雙胺基酸 (diketopiperazine) 分別為 cyclo-L-Pro-L-Val (3) 、 cyclo-L-Pro-L-Ile (4)
、 cyclo-L-Pro-L-Leu (5) 、 cyclo-D-Pro-L-Phe (6) 、 cyclo-L-Pro-L-Phe (7) 、 cyclo-L-Pr
o-L-Trp (20) 。此外,由 M1B 所分離得到的化合物在生物活性及作用機制,刻正持續探
究中。
Studies on the bioactive constituents of three marine bacterial species isolated in Taiwan
In this study, 143 strains of marine bacteria isolated from Taiwan were cultured for
the screening of their inducible nitric oxide synthase (iNOS) inhibitory activity and
vasorelaxing activity. Of these bacterial strains monitored, HYC21 (Streptomyces s
p.) and HYC13 (Pseudoalteromonas sp.) exhibited cytotoxic activities against RA
W 264.7 cell line. While M1B (Pseudomonas aeruginosa) exhibited vasorelaxing ac
tivity on Sprague-Dawley rats induced by phenylephrine. Based on these findings, t
he three strains were thus mass cultured and a series of separation and isolation wer
e undertaken to investigate their active principles. Totally twenty-one compounds i
ncluding 2 cyclic peptide antibiotics, 2 polybrominated phenolic antibiotics, 3 choli
c acid and its analogs, 5 quinoline alkaloids, 2 phenolics, a phenazine alkaloid, and
6 diketopiperazine was isolated and identified. Their structures were elucidated to b
e actinomycin X2 (1), actinomycin D (2), cyclo-L-Pro-L-Val (3), cyclo-L-Pro-L-Ile
(4), cyclo-L-Pro-L-Leu (5), cyclo-D-Pro-L-Phe (6), cyclo-L-Pro-L-Phe (7), pentabr
omopseudilin (8), 3,3′,5,5′-tetrabromo-2,2′-biphenyldiol (9), cholic acid (10), deoxy
cholic acid (11), glycocholic acid (12), 2-heptylquinol-4-one (13), 2-heptyl-3-hydro
xyquinolin-4(1H)-one (14), 2- (1′E-nonenyl)quinol-4-one (15), 2-nonylquinol-4-on
e (16), 3- heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione (17), 2-(2-hydrox
yphenyl)-2-thiazoline-4-methanol (18), 4,4′-isopropylidenebisphenol (19), cyclo-L-
Pro-L-Trp (20), phenazine-1-carboxamide (21).