Monascus spp. produce several well-known polyketides such as monacolin K, citrinin, and azaphilone pigments. In this study, the azaphilone pigment biosynthetic gene cluster was identified through T-DNA random mutagenesis in Monascus purpureus. The albino mutant W13 bears a T-DNA insertion upstream of a transcriptional regulator gene (mppR1). The transcription of mppR1 and the nearby polyketide synthase gene (MpPKS5) was significantly repressed in the W13 mutant. Targeted inactivation of MpPKS5 also gave rise to an albino mutant, confirming that mppR1 and MpPKS5 belong to an azaphilone pigment biosynthetic gene cluster. This M. purpureus sequence was used to identify the whole biosynthetic gene cluster in the Monascus pilosus genome. MpPKS5 contains SAT/KS/AT/PT/ACP/MT/R domains, and this domain organization is preserved in other azaphilone polyketide synthases. This biosynthetic gene cluster also encodes fatty acid synthase (FAS), which is predicted to assist the synthesis of 3-oxooactanoyl-CoA and 3-oxodecanoyl-CoA. These 3-oxoacyl compounds are proposed to be incorporated into the azaphilone backbone to complete the pigment biosynthesis. A monooxygenase gene (an azaH and tropB homolog) that is located far downstream of the FAS gene is proposed to be involved in pyrone ring formation. A homology search on other fungal genome sequences suggests that this azaphilone pigment gene cluster also exists in the Penicillium marneffei and Talaromyces stipitatus genomes.
Alternative splicing is a major diversification mechanism in the human transcriptome and proteome. Several diseases, including cancers, have been associated with dysregulation of alternative splicing. Thus, correcting alternative splicing may restore normal cell physiology in patients with these diseases. This paper summarizes several alternative splicing-related diseases, including cancers and their target genes. Since new cancer drugs often target spliceosomes, several clinical drugs and natural products or their synthesized derivatives were analyzed to determine their effects on alternative splicing. Other agents known to have modulating effects on alternative splicing during therapeutic treatment of cancer are also discussed. Several commonly used bioinformatics resources are also summarized.
A string-matching engine capable of inspecting multiple characters in parallel can multiply the throughput. However, the space required for implementing a matching engine that can process multiple characters in parallel generally grows exponentially with respect to the characters to be processed in parallel. Based on the Aho-Corasick algorithm (AC-algorithm), this work presents a novel multicharacter transition Nondeterministic Finite Automaton (NFA) approach, called
multicharacter AC-NFA
, to allow for the inspection of multiple characters in parallel. This approach first converts an AC-trie to an AC-NFA by allowing for the simultaneous activation of multiple states and then converts the AC-NFA to a
k
-character AC-NFA by an algorithm with concatenation operations and assistant transitions. Additionally, the alignment problem, which occurs while multiple characters are being inspected in parallel, is solved using assistant transitions. Moreover, a corresponding output is provided for each inspected character by introducing priority multiplexers to determine the final matching outputs during implementation of the multicharacter AC-NFA. Consequently, the number of derived
k
-character transitions grows linearly with respect to the number
k
. Furthermore, the derived multicharacter AC-NFA is implemented on FPGAs for evaluation. The resulting throughput grows approximately 14 times and the hardware cost grows about 18 times for 16-character AC-NFA implementation, as compared with that for 1-character AC-NFA implementation. The achievable throughput is 21.4Gbps for the 16-character AC-NFA implementation operating at a 167.36MHz clock.
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