Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes
Jia Tang,Yudai Matsuda +1 more
TLDR
The tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways are characterized.Abstract:
The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized via the cyclization of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many products, only three cyclization modes have been reported. Here, we discovered a meroterpenoid biosynthetic gene cluster in Aspergillus insuetus CBS 107.25, which encodes the biosynthetic enzymes for 1 along with a terpene cyclase that is phylogenetically distantly related to the other characterized cyclases of 1. Intriguingly, InsA7, the terpene cyclase, folds 1 in a pre-boat-chair conformation, generating a new meroterpenoid species with an axially oriented hydroxy group at C3. The A. insuetus strain also harbors an additional gene cluster encoding another cyclase of 1. The second terpene cyclase–InsB2–also synthesizes a new cyclized product of 1, thereby leading to diverging of the biosynthetic pathway in the fungus. Finally, we characterized the tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways.read more
Citations
More filters
Journal ArticleDOI
Depside Bond Formation by the Starter-Unit Acyltransferase Domain of a Fungal Polyketide Synthase.
TL;DR: A polyketide synthase from the fungus Aspergillus duricaulis is discovered and it is determined that depside bond formation is catalyzed by the starter-unit acyltransferase (SAT) domain of DrcA, a previously undescribed form of SAT domain chemistry.
Journal ArticleDOI
Biosynthetic Characterization, Heterologous Production, and Genomics-Guided Discovery of GABA-Containing Fungal Heptapeptides.
TL;DR: In this paper , the unguisin pathway involves the alanine racemase UngC to provide d-alanine, which is then accepted by the first adenylation domain of the nonribosomal peptide synthetase (NRPS) UngA.
Journal ArticleDOI
Hot off the press.
Robert A. Hill,Andrew Sutherland +1 more
TL;DR: A personal selection of 32 recent papers covering various aspects of current developments in bioorganic chemistry and novel natural products such as anisotanol A from Anisodus tanguticus is presented in this article .
Journal ArticleDOI
Ketoreductase Domain-Catalyzed Polyketide Chain Release in Fungal Alkyl Salicylaldehyde Biosynthesis.
Run-Qing Yang,Jian Feng,Bin Cheng,Yan-Ping Li,Hang Wang,Qiu-Fen Hu,Wei-Lie Xiao,Yudai Matsuda,Weiguang Wang +8 more
TL;DR: In this article , the authors discovered an orphan biosynthetic gene cluster of salicylaldehyde derivatives in the fungus Stachybotrys sp. g12, which encoded a highly reducing PKS StrA, encoded by the gene cluster, performs a reductive polyketide chain release, although it lacks a C-terminal reductase domain, which is typically required for such a reductive release.
Journal ArticleDOI
Dissection of the Catalytic Mechanisms of Transmembrane Terpene Cyclases Involved in Fungal Meroterpenoid Biosynthesis.
Jia Tang,Yudai Matsuda +1 more
TL;DR: In this paper , the authors focused on AdrI, the Pyr4-family enzyme for the andrastin A pathway, and its homologues, and performed a series of mutational experiments using their AlphaFold2-generated structures.
References
More filters
Journal ArticleDOI
Structural and Chemical Biology of Terpenoid Cyclases.
TL;DR: Key advances in terpenoid cyclase structural and chemical biology are reviewed, focusing mainly on ter penoid cyclases and related prenyltransferases for which X-ray crystal structures have informed and advanced the authors' understanding of enzyme structure and function.
Journal ArticleDOI
Meroterpenoids produced by fungi
Regina Geris,Thomas J. Simpson +1 more
TL;DR: This review deals with the isolation and structure elucidation of meroterpenoids from higher and lower fungi, and discusses biosynthetic studies and biological activities as appropriate.
Journal ArticleDOI
Biosynthesis of fungal meroterpenoids
Yudai Matsuda,Ikuro Abe +1 more
TL;DR: This review summarizes the molecular bases for their biosyntheses, which were recently elucidated with modern techniques, and also discusses the plausible biosynthetic pathways of other related natural products lacking genetic information.
Journal ArticleDOI
Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases
Takayuki Itoh,Kinya Tokunaga,Yudai Matsuda,Isao Fujii,Ikuro Abe,Yutaka Ebizuka,Tetsuo Kushiro,Tetsuo Kushiro +7 more
TL;DR: The successful production of a pyripyropene analogue illustrates the catalytic versatility of these enzymes for the production of novel analogues with useful biological activities.
Journal ArticleDOI
Development of a novel quadruple auxotrophic host transformation system by argB gene disruption using adeA gene and exploiting adenine auxotrophy in Aspergillus oryzae
TL;DR: Results obtained showed that the adeA gene served as an efficient selection marker in developing a novel host-vector system with quadruple auxotrophy in A. oryzae, thus providing a powerful tool to breed multiple auxotrophic mutants from a deuteromycete wherein sexual crossing is impossible.