Heterologous expression of the trichostatin gene cluster and functional characterization ofN-methyltransferase TsnB8

Abstract

N-Methyltransferase TsnB8 was demonstrated to catalyze successive methyltransfer reactions in the biosynthesis of trichostatin.

Ulleunganilines A–C, Trichostatin Analogues Bearing a Modified Side Chain from Streptomyces sp. 13F051

“…23−25 The olefin group of the released intermediate is then reduced by an unknown enol reductase (ER), followed by two methyl transfer reactions catalyzed by N-methyltransferase (tsnB8), which convert the formed intermediate to 2 and subsequently to 1. 4 In the second case, 1 and 2 could be formed by the enzymatic degradation of TSA. This hypothesis is based on the isolation of dehydroxytrichostatin A (8), which has a short branched carbon chain compared to TSA, and the results of the previous study on mice, 20 suggesting that 1 is produced due to biodegradation of TSA.…”

“…Additional modification genes were also found to be involved in the formation of trichostatin analogues. 3,4 In this study, we found that, in addition to compounds 1 and 2, Streptomyces sp. 13F051 also produces trichostatin analogues 3−10, which bear an additional propionate unit in the branched carbon chain.…”

“…Specifically, it was found that tsn B polyketide synthase (PKS) employs p -aminobenzoic acid as a starter unit and TSA originates from a trimodular PKS pathway. Additional modification genes were also found to be involved in the formation of trichostatin analogues. , In this study, we found that, in addition to compounds 1 and 2 , Streptomyces sp. 13F051 also produces trichostatin analogues 3 – 10 , which bear an additional propionate unit in the branched carbon chain.…”

“…has also been recently identified, and the biosynthetic origins of the hydroxamate and N,N-dimethyl groups have been established in detail. 3,4 Moreover, due to the promising properties of TSA, numerous studies have focused on identifying novel trichostatin analogues, some of which have been isolated from Streptomyces sp. 4−15 In a previous study, we investigated the chemical profiles of actinomycetes isolated from soil samples at Ulleung Island by PDA-LC-MS. 16 In particular, we found that, among the 208 isolated actinomycete strains, Streptomyces sp.…”

“…The complete TSA biosynthetic gene cluster from Streptomyces sp. has also been recently identified, and the biosynthetic origins of the hydroxamate and N , N -dimethyl groups have been established in detail. , Moreover, due to the promising properties of TSA, numerous studies have focused on identifying novel trichostatin analogues, some of which have been isolated from Streptomyces sp. − …”