Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• the nascent NP rather than its chain extension, or utilized iteratively [22][23]. In textbook assembly line-like pathways, the architecture of the mega enzyme complex correlates with the product structure, a principle that is referred to as the colinearity rule [24]. Examples of these assembly line

• harbor non-canonical module architectures and cryptic domains [19][22]. As a result, the colinearity rule cannot be applied to predict trans-AT PKS-derived polyketide core structures [19]. Instead, it has been observed that the amino acid sequences of the ketosynthase domains in trans-AT PKSs correlate

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• thiotemplate biosynthetic pathways that enable relatively precise predictions of natural product core structures (e.g., the colinearity rule in NRPSs and cis-acyltransferase polyketide synthases [8]), no such rules exist for the predictions of the cyclic hydrocarbon backbone produced by TCs [1]. This is likely

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm. Keywords: colinearity; ebelactone; enzyme catalysis

• the eventual product is often referred to as colinearity. Each module contains a ketosynthase (KS) domain, which recruits the growing polyketide acyl chain from the previous module and catalyses its Claisen-like carbon–carbon bond condensation with the incoming (alkyl)malonyl extender unit, tethered

• from colinearity are those where the number of modules in the PKS does not correspond to the number of extension units found in the chemical product [10][12]. Strains subjected either to random mutagenesis or to a targetted block in post-PKS steps have been found to accumulate aberrant products of

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• modules, each being responsible for the incorporation of a single amino acid. The order of these modules typically follows a colinearity rule, i.e., the succession of modules corresponds to the order of amino acids in the final product. A minimal module is composed of an amino acid-activating adenylation