Cryptic Production of trans-3-Hydroxyproline in Echinocandin B Biosynthesis.
Cryptic Production of trans-3-Hydroxyproline in Echinocandin B Biosynthesis.
Appl Environ Microbiol. 2018 Jan 19;:
Authors: Mattay J, Houwaart S, Hüttel W
Abstract
Echinocandins are antifungal nonribosomal hexapeptides produced by fungi. Two of the amino acids are hydroxy-l-prolines: trans-4-hydroxy-l-proline and, in most echinocandin structures, (trans-2,3)-3-hydroxy-(trans-2,4)-4-methyl-l-proline. In the case of echinocandin biosynthesis by Glarea lozoyensis, both amino acids are found in pneumocandin A0, while in pneumocandin B0 the latter residue is substituted by trans-3- hydroxy-l-proline (3-Hyp). We have recently reported that all three amino acids are generated by the 2-oxoglutarate-dependent proline hydroxylase GloF. In echinocandin B biosynthesis by Aspergillus species, 3-Hyp derivatives have not been reported. Here, we describe the heterologous production and kinetic characterization of HtyE, the 2-oxoglutarate dependent proline hydroxylase from the echinocandin B biosynthetic cluster in Aspergillus pachycristatus Surprisingly, l-proline hydroxylation with HtyE resulted in an even higher proportion (∼30%) of 3-Hyp than that with GloF. This suggests that the selectivity for methylated 3-Hyp in echinocandin B biosynthesis is solely due to a substrate specific adenylation domain of the nonribosomal peptide synthetase. Moreover, we observed that one product of HtyE catalysis, 3-hydroxy-4-methyl-l-proline, is slowly further ...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Mattay J, Houwaart S, Hüttel W Tags: Appl Environ Microbiol Source Type: research
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