• Natural Product Sciences
• /
• 제21권4호
• /
• pp.231-236
• /
• 2015

Two new azaphilone derivatives containing 1,3-dioxolane moiety, penidioxolanes A (1) and B (2), were isolated from marine-derived fungus Penicillium sp. KCB12C078, together with four known compounds (3-6) by chemical investigation. Compounds 1 - 6 were isolated by combination of silica gel, ODS column chromatography and preparative HPLC. Their structures were determined by analysis of spectroscopic data including 1D-, 2D-NMR, and MS techniques. The isolates were evaluated against cancer cell growth inhibition effects and antimicrobial activity.

• Journal of Applied Biological Chemistry
• /
• 제60권3호
• /
• pp.249-256
• /
• 2017

The Monascus azaphilone (MAz) pigment is a well-known food colorant that has yellow, orange and red components. The structures of the yellow and orange MAz differ by two hydride reductions, with yellow MAz being the reduced form. Orange MAz can be non-enzymatically converted to red MAz in the presence of amine derivatives. It was previously demonstrated that mppE and mppG are involved in the biosynthesis of yellow and orange MAz, respectively. However, ${\Delta}mppE$ and ${\Delta}mppG$ knockout mutants maintained residual production of yellow and orange MAz, respectively. In this study, we deleted the region encompassing mppD, mppE and mppG in M. purpureus and compared the phenotype of the resulting mutant (${\Delta}mppDEG$) with that of an mppD knockout mutant (${\Delta}mppD$). It was previously reported that the ${\Delta}mppD$ strain retained the ability to produce MAz but at approximately 10% of the level observed in the wildtype strain. A chemical analysis demonstrated that the ${\Delta}mppDEG$ strain was still capable of producing both yellow and orange MAz, suggesting the presence of minor MAz route(s) not involving mppE or mppG. Unexpectedly, the ${\Delta}mppDEG$ strain was observed to accumulate fast-eluting pigments in a reverse phase high-performance liquid chromatography analysis. A LC-MS analysis identified these pigments as ethanolamine derivatives of red MAz, which had been previously identified in an mppE knockout mutant that produces high amounts of orange MAz. Although the underlying mechanism is largely unknown, this study has yielded an M. purpureus strain that selectively accumulates red MAz.

• Mycobiology
• /
• 제47권2호
• /
• pp.256-260
• /
• 2019

Neuraminidase (NA) cleaves the glycosidic bond linkages of sialic acids to release the mature virions from infected cells and has been an attractive therapeutic target for anti-influenza agents. In our ongoing investigation of NA inhibitors in mushroom extracts, we found that the extract the fruiting body of Glaziella splendens potently inhibited neuraminidase. The fruiting bodies of G. splendens were extracted and partitioned successively with hexane, ethyl acetate, and butanol. The ethyl acetate soluble-layer was subjected to silica gel and Sephadex LH-20 column chromatographies, and MPLC to obtain five compounds (1-5). Their structures were determined by spectroscopic methods. NA inhibitory activity of these compounds was evaluated using NAs from recombinant rvH1N1, H3N2, and H5N1 influenza A viruses. One compound (1) was elucidated as a new azaphilone derivative, and four compounds (2-5) were identified as entonaemin A, comazaphilone D, rubiginosin A, and entonaemin B, respectively. Compounds 3 and 4 showed considerable inhibitory activity against three types of neuraminidases with the $IC_{50}$ values of 30.9, 41.8, and $35.7{\mu}M$ for 3 and 46.5, 50.4, and $29.9{\mu}M$ for 4, respectively. This study reveals that the fruiting bodies of G. splendens possess azaphilone derivatives with the NA inhibitory activity. This is the first report on the isolation of neuraminidase inhibitors from the fruiting bodies of G. splendens.

• Journal of Applied Biological Chemistry
• /
• 제61권1호
• /
• pp.83-91
• /
• 2018

박테리아와 진균의 유전체 정보 탐색을 통하여 이차대사 생합성을 지정하는 다수의 잠재 유전자군을 찾을 수 있으며, 유전체 정보를 기반으로 특정 유전자의 발현을 활성화하여 잠재 유전자군의 생성물을 추론하고, 해당 물질의 생물학적 기능을 연구하는 것이 가능하다. 동아시아 지역에서 잘 알려진 식용 사상진균 홍국에 대하여 몇 몇 유전체 정보가 공개되어있으며, 본 연구에서는 Monascus purpureus ${\Delta}MpPKS5$ 균주에서 polyketide synthase-nonribosomal peptide synthase 유전자 Mpfus1 상단에 Aspergillus gpdA 프로모터를 삽입하는 방식으로 이 유전자의 발현을 활성화하였다. Mpfus1 유전자군은 2-pyrrolidone/conjugated polyene 구조를 갖는 물질의 생합성 유전자군들과 높은 유사성을 보이며, 이들 화합물 그룹에서 진균 독소인 fusarin이 잘 알려져 있다. ${\Delta}MpPKS5$ 균주는 홍국 azaphilone 색소 생산 능력이 소실된 균주이며 색소 및 자외선 흡수 특성을 보이는 화합물들의 동정에 적절한 균주이다. Mpfus1 활성화는 균사체가 노란색을 띠도록 유도하며, 균사체의 methanol 추출액은 365 nm에서 최대 흡광도를 보임을 확인할 수 있었다. 해당 추출액의 HPLC 분석을 통하여 다수의 화합물들이 포함되어 있음을 확인할 수 있었으며 이를 통하여 MpFus1 효소의 생성물이 대사적, 화학적으로 불안정함을 추론할 수 있다. Mpfus1 활성화 균주 추출물을 LC-MS로 분석하여 MpFus1 생성물의 구조를 유추하여 Mpfus1 유전자군이 fusarin의 탈메틸 유사체 생합성을 지정하는 것으로 제안할 수 있었다. 본 연구는 홍국 균주에서 유전체 기반-미지 화합물 발굴 연구의 예를 제시하고 홍국 균주에서 새로운 생리활성의 동정 가능성을 시사하여 준다.