Identification of the pyranonigrin A biosynthetic gene cluster by genome mining in Penicillium thymicola IBT 5891

Abstract

Significance A polyketide synthase and nonribosomal peptide synthetase hybrid gene cluster from the genome of Penicillium thymicola was identified through genome mining. Heterologous expression of this cluster leads to the production of pyranonigrin A. A series of experiments established that only four genes are sufficient to biosynthesize pyranonigrin A. Based on the results from the current study, a biosynthetic pathway of pyranonigrin A is proposed. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4182–4186, 2018

Predicting the chemical space of fungal polyketides by phylogeny-based bioinformatics analysis of polyketide synthase-nonribosomal peptide synthetase and its modification enzymes

“…For pyranonigrin clade identification, we selected two key modification enzymes (MEs), FMO and P450, by considering the biosynthetic pathway of pyranonigrins (Schemes 3 and S2, Fig. 1, and Table S2) [26][27][28] . A local BLAST search of FMO/P450 using our hybrid library (884 BGCs) identified 79 BGCs (identities > 40%), which are most likely responsible for the production of various pyranonigrins.…”

Alkaloids from Marine Fungi: Promising Antimicrobials

“…By applying a high-confidence/low-novelty algorithm, known BGCs can be detected with high accuracy. For example, Tang and colleagues used antiSMASH to predict BGCs in the genome of Penicillium thymicola IBT 5891, which eventually led to the discovery of the pyranonigrin A biosynthesis gene cluster [48]. Other tools include NaPDoS, which uses the same principle as antiSMASH but is primarily focused at secondary metabolites with polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) in their corresponding pathways, and 2ndFind, a web-based secondary metabolite BGC finder.…”

“…Starting materials for pyranonigrin A are one unit of acetyl-CoA, three units of malonyl-CoA, and one unit of l-glycine [59], whereas pyranonigrin E is biosynthesized from six malonyl-CoA, one acetyl-CoA, and one l-serine unit [58]. The pyranonigrin A biosynthesis gene cluster (BGC) of P. thymicola consists of four genes, of which only three are essential for pyranonigrin A production [48]. The polyketide synthase non-ribosomal peptide synthetase (PKS-NRPS) pyrA produces a tetramic acid intermediate, possibly in conjuncture with the adscititious hydrolase pyrD.…”

“…Subsequently, the flavin-dependent monooxygenase pyrC performs an epoxidation-mediated cyclization resulting in the pyrano [2,3-c]pyrrole skeleton. The cytochrome P450 oxidase pyrB finally carries out a dehydrogenation and a hydroxylation to obtain pyranonigrin S and A, respectively [48,59]. On the other hand, the biochemical synthesis of pyranonigrin E is more complex.…”

Nonribosomal peptides in fungal cell factories: from genome mining to optimized heterologous production

“…Filamentous fungi are considered as prolific producers of NRPs. A large number of clusters involved in NRP synthesis has been detected for example in Penicillium thymicola (17 clusters), Aspergillus fumigatus (14 clusters), Talaromyces islandicus, Beauveria bassiana (13 clusters), and Pestalotiopsis fici (12 clusters) (Chiang et al, 2014;Gibson et al, 2014;Schafhauser et al, 2016;Tang et al, 2018;Wang et al, 2015). The high potential of fungal organisms for NRPs production can be exploited for the discovery of novel compounds of interest.…”