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Discussion
The global antifungal market was estimated at $9.4 billion in 2010 and is expected to grow at a rate of 1.9%
during 2010-2017. The major class of antifungal compound includes azoles, polyenes, pyrimidines, allyamines
and echinodians. The antifungal therapies intend eradicating fungi through several action mechanisms, mainly
involving destruction of cell wall and inhibition of cell division. There is a significant unmet need of novel anti-
fungal compounds, because the present portfolio of treatments interact unfavorably with other medication, have
resistance problem, low spectrum of activity, are fungistatic as opposed to fungicidal and are often toxic. Hence
research has been focused on development of potent and safe antifungal compounds, either synthetic or from
microbial sources [24]. In the present study, we exploited the marine resources for isolation of actinomycetes
strains producing antifungal compounds. In the course of study, the marine invertebrate associated active acti-
nomycetes strain PM0525875 was isolated and identified as Actinoalloteichus cyanogriseus. The antifungal
principle from this strain was characterized as Caerulomycin A that showed potent in-vitro activity against pathogenic and drug resistant Candida strains.
Caerulomycin A was first isolated from S. caeruleus [25] [26] as an antibiotic. Later it was reported to have
anti-cancer activity [27]. In-vitro and in-vivo activity of Caerulomycin A against Entamoeba histolytica has been
reported [28]. Natural derivatives of Caerulomycin A has also been reported [29]. Caerulomycin B and C, a new
2,2′-dipyridyl derivatives were isolated from Streptomyces caeruleus supplemented with 1 mM L-tryptophan.
This group also reported the isolation of Caerulomycin D [19]. Additional natural derivatives of Caerulomycin
F-K were isolated from marine derived actinomycetes (Actinoalloteichus cyanogriseus) that showed anticancer
and antibacterial activity [29]. Lin et al. identified the biosynthetic gene cluster for Caerulomycin A from ma-
rine actinomycetes Actinoalloteichus cyanogriseus. It mainly consists of unusual hybrid polyketide synthase
(PKS) and nonribosomal peptide synthetase (NRPS) [30]. The biosynthesis of Caerulomycin A based on enzy-
matic modifications leading to structural changes, have been studied [31]. Chemical synthesis of Caerulomycin
A-C has also been reported [32] [33]. The immunosuppressive activity of Caerulomycin A and its natural ana-
logues has been reported [34].
Although Caerulomycin A has not been entered in clinic so far, may be due to its limitations, it could be the
ideal molecule for generating semi synthetic druggable derivatives having potential application as an anticancer,
antifungal or immunosuppressive drug. The strain and the optimized fermentation process described here could
be useful for large scale production of this molecule for further drug development studies.
5. Conclusion
In our in-house screening program in the quest of novel and superior antifungal compounds, an actinomycetes
strain PM0525875 was isolated from a marine invertebrate. The active principle was characterized to be Caeru-
lomycin A. Minimum inhibitory concentration (MIC) of the compound was found in the range of 0.39 - 1.56
μg/ml against pathogenic fungal test strains. The phylogenetic analysis of producer strain using 16S rRNA se-
quence showed closest match with Actinoalloateichus cyanogriseus. Overall, Caerulomycin A was isolated from
marine invertebrate-associated Actinoalloteichus sp. using optimized medium and fermentation conditions.

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討論
2010年的評估指出抗菌劑的全球市場值為94億美元，而且從2010年至2017年間會以1.9%的速率不斷增長�？咕鷦┑闹饕煞趾蝾�、多烯類、嘧啶類、以及烯胺類 �？拐婢煼ㄔ噲D通過多種作用機制—主要是破壞細胞壁及抑制細胞的分解—來根除真菌。新型抗真菌化合物的需求量遠未得到滿足，其原因是現(xiàn)有的組合療法內(nèi)部機制間存在相互抵制，且作用范圍小，其與抗菌劑的作用相悖，甚至會使抗菌劑失效。
因而有研究致力于開發(fā)高效、安全的抗真菌化合物，包括合成及從細菌中提取[24]。在本研究中，我們開發(fā)利用了細菌源進行放線菌株的隔離，來制取抗真菌化合物。我們在試驗中將海洋無脊椎動物的相關抗菌性菌株進行了隔離，并確定其為海洋來源放線菌。該菌株的抗菌性原理類似于淺藍霉素 A，其對致病性和耐藥性念珠菌菌株表現(xiàn)出很強的體外活性。
淺藍霉素 A是一種首次由S. caeruleus [25] [26]分離的抗生素。之后有報道稱其有抗癌作用[27]。淺藍霉素 A的體內(nèi)抗痢疾變形蟲作用已經(jīng)報道[28]。還有報道指出淺藍霉素 A的人工合成方法[29]。

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